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

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: mouse all
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Genomic context

Location:: 10q11.21

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (44370165..44385097, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (45251013..45265954, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (44865613..44880545, complement)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

CXCL12 Gene Polymorphisms and Serum Levels: Associations with Multiple Sclerosis Prevalence and Clinical Parameters in Lithuania.
Title: CXCL12 Gene Polymorphisms and Serum Levels: Associations with Multiple Sclerosis Prevalence and Clinical Parameters in Lithuania.
Fast H3K9 methylation promoted by CXCL12 contributes to nuclear changes and invasiveness of T-acute lymphoblastic leukemia cells.
Title: Fast H3K9 methylation promoted by CXCL12 contributes to nuclear changes and invasiveness of T-acute lymphoblastic leukemia cells.
A NOTCH3-CXCL12-driven myeloma-tumor niche signaling axis promotes chemoresistance in multiple myeloma.
Title: A NOTCH3-CXCL12-driven myeloma-tumor niche signaling axis promotes chemoresistance in multiple myeloma.
Cadherin-6 is a novel mediator for the migration of mesenchymal stem cells to glioblastoma cells in response to stromal cell-derived factor-1.
Title: Cadherin-6 is a novel mediator for the migration of mesenchymal stem cells to glioblastoma cells in response to stromal cell-derived factor-1.
PON1, APOE and SDF-1 Gene Polymorphisms and Risk of Retinal Vein Occlusion: A Case-Control Study.
Title: PON1, APOE and SDF-1 Gene Polymorphisms and Risk of Retinal Vein Occlusion: A Case-Control Study.
SDF-1 promotes metastasis of NSCLC by enhancing chemoattraction of megakaryocytes through the PI3K/Akt signaling pathway.
Title: SDF-1 promotes metastasis of NSCLC by enhancing chemoattraction of megakaryocytes through the PI3K/Akt signaling pathway.
ABCF1/CXCL12/CXCR4 Enhances Glioblastoma Cell Proliferation, Migration, and Invasion by Activating the PI3K/AKT Signal Pathway.
Title: ABCF1/CXCL12/CXCR4 Enhances Glioblastoma Cell Proliferation, Migration, and Invasion by Activating the PI3K/AKT Signal Pathway.
CXCL12-CXCR4 mediates CD57[+] CD8[+] T cell responses in the progression of type 1 diabetes.
Title: CXCL12-CXCR4 mediates CD57(+) CD8(+) T cell responses in the progression of type 1 diabetes.
Diagnostic and prognostic utility of TROP-2, SLP-2, and CXCL12 expression in papillary thyroid carcinoma.
Title: Diagnostic and prognostic utility of TROP-2, SLP-2, and CXCL12 expression in papillary thyroid carcinoma.
Association of the CXCL12 rs1801157 Polymorphism with Breast Cancer Risk: A Meta-Analysis.
Title: Association of the CXCL12 rs1801157 Polymorphism with Breast Cancer Risk: A Meta-Analysis.

Submit: New GeneRIF Correction See all GeneRIFs (1262)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

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

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D10S2188 (e-PCR)
- UniSTS:38915

G30000 (e-PCR)
- UniSTS:77584

D10S1350E (e-PCR)
- UniSTS:151362

G17474 (e-PCR)
- UniSTS:2886

SGC33589 (e-PCR)
- UniSTS:81058

RH44690 (e-PCR)
- UniSTS:26280

SGC33789 (e-PCR)
- UniSTS:54469

RH44662 (e-PCR)
- UniSTS:62715

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 T cell chemotaxis	IDA Inferred from Direct Assay 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 antimicrobial humoral immune response mediated by antimicrobial peptide	IDA Inferred from Direct Assay more info	PubMed
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 killing of cells of another organism	IDA Inferred from Direct Assay 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

Component	Evidence Code	Pubs
located_in collagen-containing extracellular matrix	HDA more info	PubMed
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info

General protein information

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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)

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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

NG_016861.2 RefSeqGene

Range

5001..13031

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000609.7 → NP_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:27 → 88

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 ...
NM_001033886.2 → NP_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:27 → 88

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 ...
NM_001178134.2 → NP_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:27 → 88

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 ...
NM_001277990.2 → NP_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
NM_199168.4 → NP_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:27 → 88

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 ...