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

Gene ID: 6387, updated on 19-Feb-2024

Summary

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 MIM:600835; AllianceGenome:HGNC:10672
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]
Expression
Broad expression in endometrium (RPKM 50.4), spleen (RPKM 44.2) and 23 other tissues See more
Orthologs
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Genomic context

See CXCL12 in Genome Data Viewer
Location:
10q11.21
Exon count:
6
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (44370165..44385097, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (45251013..45265954, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (44865613..44880545, complement)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124902543 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:44607592-44608157 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_12798 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_12804 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr10:44664362-44665561 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_12892 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:44688953-44689454 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:44689455-44689954 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_12920 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3307 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:44703238-44703811 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:44728896-44729550 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:44729551-44730205 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr10:44730206-44730859 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_13072 Neighboring gene VISTA enhancer hs2509 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3311 Neighboring gene uncharacterized LOC124902544 Neighboring gene NANOG hESC enhancer GRCh37_chr10:44793368-44793869 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr10:44796158-44797357 Neighboring gene long intergenic non-protein coding RNA 2881 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3312 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:44805333-44805502 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:44806263-44806765 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3313 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2339 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:44821405-44821620 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:44833715-44834216 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:44852471-44853402 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:44859545-44860046 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:44860047-44860546 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:44866272-44866820 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:44873825-44874771 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:44878101-44878794 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:44878795-44879488 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:44879489-44880180 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2340 Neighboring gene uncharacterized LOC107984179 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:44890534-44891279 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:44891280-44892024 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:44894259-44895003 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:44895004-44895748 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:44895749-44896492 Neighboring gene ribosomal protein L9 pseudogene 21

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Susceptibility to HIV infection
MedGen: C1836230 OMIM: 609423 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

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

HIV-1 interactions

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

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables CXCR chemokine receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
 
enables CXCR chemokine receptor binding IDA
Inferred from Direct Assay
more info
PubMed 
enables chemokine activity IBA
Inferred from Biological aspect of Ancestor
more info
 
enables chemokine activity IDA
Inferred from Direct Assay
more info
PubMed 
enables chemokine activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
enables chemokine activity TAS
Traceable Author Statement
more info
PubMed 
enables chemokine receptor binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
enables growth factor activity IEA
Inferred from Electronic Annotation
more info
 
enables integrin binding IDA
Inferred from Direct Assay
more info
PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables signaling receptor binding TAS
Traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
involved_in CXCL12-activated CXCR4 signaling pathway IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in G protein-coupled receptor signaling pathway TAS
Traceable Author Statement
more info
PubMed 
involved_in adult locomotory behavior IEA
Inferred from Electronic Annotation
more info
 
involved_in animal organ regeneration IEA
Inferred from Electronic Annotation
more info
 
involved_in axon guidance IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in blood circulation TAS
Traceable Author Statement
more info
PubMed 
involved_in cell adhesion TAS
Traceable Author Statement
more info
PubMed 
involved_in cell chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in cell chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
involved_in cellular response to chemokine IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in chemokine (C-X-C motif) ligand 12 signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in chemokine-mediated signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in chemokine-mediated signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
involved_in chemotaxis TAS
Traceable Author Statement
more info
PubMed 
involved_in defense response IEA
Inferred from Electronic Annotation
more info
 
involved_in detection of mechanical stimulus involved in sensory perception of pain IEA
Inferred from Electronic Annotation
more info
 
involved_in detection of temperature stimulus involved in sensory perception of pain IEA
Inferred from Electronic Annotation
more info
 
involved_in immune response IEA
Inferred from Electronic Annotation
more info
 
involved_in induction of positive chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in integrin activation IDA
Inferred from Direct Assay
more info
PubMed 
involved_in intracellular calcium ion homeostasis TAS
Traceable Author Statement
more info
PubMed 
involved_in negative regulation of dendritic cell apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of leukocyte tethering or rolling IDA
Inferred from Direct Assay
more info
PubMed 
involved_in neuron migration IEA
Inferred from Electronic Annotation
more info
 
acts_upstream_of_or_within positive regulation of T cell migration IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of axon extension involved in axon guidance IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of calcium ion import TAS
Traceable Author Statement
more info
PubMed 
acts_upstream_of_or_within positive regulation of cell adhesion IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of cell migration IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in positive regulation of dopamine secretion IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of endothelial cell proliferation IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of monocyte chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of neuron differentiation IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of vasculature development IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in regulation of actin polymerization or depolymerization TAS
Traceable Author Statement
more info
PubMed 
involved_in response to hypoxia IEA
Inferred from Electronic Annotation
more info
 
involved_in response to peptide hormone IEA
Inferred from Electronic Annotation
more info
 
involved_in response to ultrasound IEA
Inferred from Electronic Annotation
more info
 
involved_in response to virus TAS
Traceable Author Statement
more info
PubMed 
involved_in signal transduction TAS
Traceable Author Statement
more info
PubMed 
involved_in telencephalon cell migration IEA
Inferred from Electronic Annotation
more info
 

General protein information

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

NCBI Reference Sequences (RefSeq)

NEW Try the new Transcript table

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_016861.2 RefSeqGene

    Range
    5001..13031
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000609.7NP_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)
    AL137026
    Consensus CDS
    CCDS44373.1
    UniProtKB/Swiss-Prot
    B2R4G0, E7EVL0, H7BYN8, P48061, Q2L985, Q2L986, Q2L988, Q5IT36, Q6ICW0, Q9H554
    Related
    ENSP00000363551.2, ENST00000374429.6
    Conserved Domains (1) summary
    cd00273
    Location:2788
    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 contain an RCxC motif ...
  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
    ENSP00000363548.2, ENST00000374426.6
    Conserved Domains (1) summary
    cd00273
    Location:2788
    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 contain an RCxC motif ...
  3. NM_001178134.2NP_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
    ENSP00000379140.2, ENST00000395794.2
    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_001277990.2NP_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)
    AL137026
    Consensus CDS
    CCDS60518.1
    UniProtKB/Swiss-Prot
    P48061
    Related
    ENSP00000379139.3, ENST00000395793.7
  5. NM_199168.4NP_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
    ENSP00000339913.6, ENST00000343575.11
    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: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

    Range
    44370165..44385097 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060934.1 Alternate T2T-CHM13v2.0

    Range
    45251013..45265954 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)