1. Gene Aliases

C-X-C Motif Chemokine Ligand 1, SCYB1, NAP-3, MGSA-A, GRO1, MGSA, Chemokine (C-X-C Motif) Ligand 1, GRO1 Oncogene (Melanoma Growth Stimulating Activity, Alpha), Melanoma Growth Stimulating Activity, Alpha, Neutrophil-Activating Protein 3, Growth-Regulated Alpha Protein, Fibroblast Secretory Protein, C-X-C Motif Chemokine 1, GRO-Alpha(1-73), GROa, GROA, FSP, Melanoma Growth Stimulatory Activity Alpha, Melanoma Growth Stimulatory Activity, MGSA Alpha, GRO

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=CXCL1&keywords=Cxcl1]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

antimicrobial humoral immune response mediated by antimicrobial peptide [An immune response against microbes mediated by anti-microbial peptides in body fluid. GO:0061844]

cell chemotaxis [The directed movement of a motile cell guided by a specific chemical concentration gradient. Movement may be towards a higher concentration (positive chemotaxis) or towards a lower concentration (negative chemotaxis). GO:0060326]

cellular response to interleukin-17 [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-17 stimulus. GO:0097398]

cellular response to lipopolysaccharide [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria. GO:0071222]

chemokine-mediated signaling pathway [The series of molecular signals initiated by a chemokine binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. GO:0070098]

defense response [Reactions, triggered in response to the presence of a foreign body or the occurrence of an injury, which result in restriction of damage to the organism attacked or prevention/recovery from the infection caused by the attack. GO:0006952]

immune response [Any immune system process that functions in the calibrated response of an organism to a potential internal or invasive threat. GO:0006955]

inflammatory response [The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. GO:0006954]

neutrophil chemotaxis [The directed movement of a neutrophil cell, the most numerous polymorphonuclear leukocyte found in the blood, in response to an external stimulus, usually an infection or wounding. GO:0030593]

positive regulation of cytosolic calcium ion concentration [Any process that increases the concentration of calcium ions in the cytosol. GO:0007204]

positive regulation of hematopoietic stem cell proliferation [Any process that activates or increases the frequency, rate or extent of hematopoietic stem cell proliferation. GO:1902035]

positive regulation of neutrophil mediated killing of fungus [Any process that increases the frequency, rate or extent of the directed killing of a fungal cell by a neutrophil. GO:0070965]

positive regulation of potassium ion transport [Any process that activates or increases the frequency, rate or extent of the directed movement of potassium ions (K+) into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. GO:0043268]

positive regulation of sodium ion transport [Any process that increases the frequency, rate or extent of the directed movement of sodium ions (Na+) into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. GO:0010765]

positive regulation of superoxide anion generation [Any process that activates or increases the frequency, rate or extent of enzymatic generation of superoxide by a cell. GO:0032930]

response to amphetamine [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an amphetamine stimulus. Amphetamines consist of a group of compounds related to alpha-methylphenethylamine. GO:0001975]

response to estradiol [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of stimulus by estradiol, a C18 steroid hormone hydroxylated at C3 and C17 that acts as a potent estrogen. GO:0032355]

response to gamma radiation [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a gamma radiation stimulus. Gamma radiation is a form of electromagnetic radiation (EMR) or light emission of a specific frequency produced from sub-atomic particle interaction, such as electron-positron annihilation and radioactive decay. Gamma rays are generally characterized as EMR having the highest frequency and energy, and also the shortest wavelength, within the electromagnetic radiation spectrum. GO:0010332]

response to glucocorticoid [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a glucocorticoid stimulus. Glucocorticoids are hormonal C21 corticosteroids synthesized from cholesterol with the ability to bind with the cortisol receptor and trigger similar effects. Glucocorticoids act primarily on carbohydrate and protein metabolism, and have anti-inflammatory effects. GO:0051384]

response to lipid [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipid stimulus. GO:0033993]

response to lipopolysaccharide [Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria. GO:0032496]

response to oxygen-containing compound [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an oxygen-containing compound stimulus. GO:1901700]

signal transduction [The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.|Note that signal transduction is defined broadly to include a ligand interacting with a receptor, downstream signaling steps and a response being triggered. A change in form of the signal in every step is not necessary. Note that in many cases the end of this process is regulation of the initiation of transcription. Note that specific transcription factors may be annotated to this term, but core/general transcription machinery such as RNA polymerase should not. GO:0007165]

MSigDB Signatures:

RODWELL_AGING_KIDNEY_UP: Genes whose expression increases with age in normal kidney. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/RODWELL_AGING_KIDNEY_UP.html]

KRIEG_HYPOXIA_VIA_KDM3A: Genes dependent on KDM3A [GeneID=55818] for hypoxic induction in RCC4 cells (renal carcinoma) expressing VHL [GeneID=7428]. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KRIEG_HYPOXIA_VIA_KDM3A.html]

KRIEG_HYPOXIA_NOT_VIA_KDM3A: Genes induced under hypoxia independently of KDM3A [GeneID=55818] in RCC4 cells (renal carcinoma) expressing VHL [GeneID=7428]. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KRIEG_HYPOXIA_NOT_VIA_KDM3A.html]

WP_SPINAL_CORD_INJURY: Spinal cord injury [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_SPINAL_CORD_INJURY.html]

DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP: Genes up-regulated in HEK293 cells (embryonic kidney) at 6 h, 12 h or 24 h after infection with reovirus strain T3A (known as a strong inducer of apoptosis). [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP.html]

WP_PROSTAGLANDIN_SIGNALING: Prostaglandin signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_PROSTAGLANDIN_SIGNALING.html]

REACTOME_INNATE_IMMUNE_SYSTEM: Innate Immune System [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INNATE_IMMUNE_SYSTEM.html]

REACTOME_NEUTROPHIL_DEGRANULATION: Neutrophil degranulation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_NEUTROPHIL_DEGRANULATION.html]

WP_PLEURAL_MESOTHELIOMA: Pleural mesothelioma [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_PLEURAL_MESOTHELIOMA.html]

REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS: Class A/1 (Rhodopsin-like receptors) [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS.html]

REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS: Peptide ligand-binding receptors [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS.html]

LINDGREN_BLADDER_CANCER_CLUSTER_1_DN: Down-regulated genes whose expression profile is specific to Custer I of urothelial cell carcinoma (UCC) tumors. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/LINDGREN_BLADDER_CANCER_CLUSTER_1_DN.html]

KEGG_CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION: Cytokine-cytokine receptor interaction [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION.html]

REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM: Cytokine Signaling in Immune system [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM.html]

REACTOME_SIGNALING_BY_GPCR: Signaling by GPCR [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SIGNALING_BY_GPCR.html]

WP_CYTOKINES_AND_INFLAMMATORY_RESPONSE: Cytokines and inflammatory response [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_CYTOKINES_AND_INFLAMMATORY_RESPONSE.html]

PID_IL23_PATHWAY: IL23-mediated signaling events [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/PID_IL23_PATHWAY.html]

REACTOME_SIGNALING_BY_INTERLEUKINS: Signaling by Interleukins [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SIGNALING_BY_INTERLEUKINS.html]

REACTOME_G_ALPHA_I_SIGNALLING_EVENTS: G alpha (i) signalling events [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_G_ALPHA_I_SIGNALLING_EVENTS.html]

KEGG_NOD_LIKE_RECEPTOR_SIGNALING_PATHWAY: NOD-like receptor signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_NOD_LIKE_RECEPTOR_SIGNALING_PATHWAY.html]

WP_OVERVIEW_OF_PROINFLAMMATORY_AND_PROFIBROTIC_MEDIATORS: Overview of proinflammatory and profibrotic mediators [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_OVERVIEW_OF_PROINFLAMMATORY_AND_PROFIBROTIC_MEDIATORS.html]

NABA_SECRETED_FACTORS: Genes encoding secreted soluble factors [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/NABA_SECRETED_FACTORS.html]

REACTOME_GPCR_LIGAND_BINDING: GPCR ligand binding [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_GPCR_LIGAND_BINDING.html]

REACTOME_INTERLEUKIN_10_SIGNALING: Interleukin-10 signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INTERLEUKIN_10_SIGNALING.html]

PETROVA_ENDOTHELIUM_LYMPHATIC_VS_BLOOD_DN: Genes down-regulated in BEC (blood endothelial cells) compared to LEC (lymphatic endothelial cells). [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/PETROVA_ENDOTHELIUM_LYMPHATIC_VS_BLOOD_DN.html]

7. Gene Descriptions

NCBI Gene Summary: This antimicrobial gene encodes a member of the CXC subfamily of chemokines. The encoded protein is a secreted growth factor that signals through the G-protein coupled receptor, CXC receptor 2. This protein plays a role in inflammation and as a chemoattractant for neutrophils. Aberrant expression of this protein is associated with the growth and progression of certain tumors. A naturally occurring processed form of this protein has increased chemotactic activity. Alternate splicing results in coding and non-coding variants of this gene. A pseudogene of this gene is found on chromosome 4. [provided by RefSeq, Sep 2014]

GeneCards Summary: CXCL1 (C-X-C Motif Chemokine Ligand 1) is a Protein Coding gene. Diseases associated with CXCL1 include Bacterial Meningitis and Tonsillitis. Among its related pathways are MIF Mediated Glucocorticoid Regulation and GPCR downstream signalling. Gene Ontology (GO) annotations related to this gene include signaling receptor binding and chemokine activity. An important paralog of this gene is CXCL2.

UniProtKB/Swiss-Prot Summary: Has chemotactic activity for neutrophils. May play a role in inflammation and exerts its effects on endothelial cells in an autocrine fashion. In vitro, the processed forms GRO-alpha(4-73), GRO-alpha(5-73) and GRO-alpha(6-73) show a 30-fold higher chemotactic activity.

8. Cellular Location of Gene Product

Predicted location: Secreted [https://www.proteinatlas.org/ENSG00000163739/subcellular]

9. Mechanistic Information

Summary

The CXCL1 gene encodes for CXC motif chemokine ligand 1, which functions as a chemoattractant for neutrophils, essential cells in the immune system's response to infection and injury [CS: 10]. CXCL1's chemotactic action is a crucial mechanism by which the body concentrates immune resources at sites of tissue damage or infection, facilitating the containment and elimination of pathogens as well as the removal of cell debris [CS: 9]. Its interaction with glycosaminoglycans (GAGs) modulates its binding and activity, implying a nuanced control of immune cell trafficking during the inflammatory response [CS: 8].

In kidney disease contexts such as sepsis-associated acute kidney injury (SA-AKI), CXCL1 emerges as a central hub gene, with its upregulation signifying an intensified effort by the body to recruit neutrophils to the injured kidney [CS: 8]. This response likely aims to curtail infection spread and contain the septic reaction [CS: 8]. However, while this recruitment is beneficial for acute immune defense, persistent or deregulated CXCL1 expression can lead to an exaggerated inflammatory reaction that exacerbates kidney damage [CS: 9]. Chronic or sustained activation of the Cxcl1 gene pathway, however, becomes maladaptive, given the potent effects of neutrophils which include the release of reactive oxygen species and proteases [CS: 9].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: cervix, lymphoid tissue (tissue enhanced) [https://www.proteinatlas.org/ENSG00000163739/tissue]

Cell type enchanced: basal respiratory cells, ionocytes (group enriched) [https://www.proteinatlas.org/ENSG00000163739/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: