1. Gene Aliases

Early Growth Response 1, NGFI-A, AT225, Nerve Growth Factor-Induced Protein A, Early Growth Response Protein 1, Transcription Factor ETR103, KROX-24, ZIF-268, G0S30, TIS8, Transcription Factor Zif268, Zinc Finger Protein Krox-24, Zinc Finger Protein 225, Zinc Finger Gene 225, ZNF225, EGR-1, 225, KROX24

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=EGR1&keywords=Egr1]

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:

BMP signaling pathway [The series of molecular signals initiated by the binding of a member of the BMP (bone morphogenetic protein) family to a receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. GO:0030509]

T cell differentiation [The process in which a precursor cell type acquires characteristics of a more mature T-cell. A T cell is a type of lymphocyte whose defining characteristic is the expression of a T cell receptor complex. Note that the term 'thymocyte differentiation' was merged into this term because thymocytes are T cells, and thus the term was essentially redundant. Note that immunologists typically use the word 'development' to refer to cells of B or T cell lineages undergoing the process that GO describes as 'cell differentiation'. GO:0030217]

cellular response to antibiotic [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 antibiotic stimulus. An antibiotic is a chemical substance produced by a microorganism which has the capacity to inhibit the growth of or to kill other microorganisms. GO:0071236]

cellular response to cAMP [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 cAMP (cyclic AMP, adenosine 3',5'-cyclophosphate) stimulus. GO:0071320]

cellular response to follicle-stimulating hormone stimulus [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 follicle-stimulating hormone stimulus. GO:0071372]

cellular response to gamma radiation [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 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:0071480]

cellular response to gonadotropin stimulus [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 gonadotropin stimulus. GO:0071371]

cellular response to growth factor stimulus [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 growth factor stimulus. GO:0071363]

cellular response to heparin [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 heparin stimulus. GO:0071504]

cellular response to hyperoxia [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 stimulus indicating increased oxygen tension. GO:0071455]

cellular response to hypoxia [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 stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level.|Note that this term should not be confused with 'cellular response to anoxia ; GO:0071454'. Note that in laboratory studies, hypoxia is typically studied at O2 concentrations ranging from 0.1 - 5%. GO:0071456]

cellular response to insulin stimulus [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 insulin stimulus. Insulin is a polypeptide hormone produced by the islets of Langerhans of the pancreas in mammals, and by the homologous organs of other organisms. GO:0032869]

cellular response to interleukin-8 [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-8 stimulus. GO:0098759]

cellular response to isoquinoline alkaloid [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 isoquinoline alkaloid stimulus. An isoquinoline alkaloid is any member of a group of compounds with the heterocyclic ring structure of benzo(c)pyridine which is a structure characteristic of the group of opium alkaloids. GO:0071317]

cellular response to mechanical stimulus [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 mechanical stimulus. GO:0071260]

cellular response to mycophenolic acid [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 mycophenolic acid stimulus. GO:0071506]

cellular response to organic substance [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 organic substance stimulus. GO:0071310]

cellular response to steroid hormone stimulus [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 steroid hormone stimulus. GO:0071383]

cellular response to xenobiotic stimulus [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 stimulus from a xenobiotic, a compound foreign to the organism exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical. GO:0071466]

circadian regulation of gene expression [Any process that modulates the frequency, rate or extent of gene expression such that an expression pattern recurs with a regularity of approximately 24 hours. GO:0032922]

circadian rhythm [Any biological process in an organism that recurs with a regularity of approximately 24 hours. GO:0007623]

circadian temperature homeostasis [Any homeostatic process in which an organism modulates its internal body temperature at different values with a regularity of approximately 24 hours. GO:0060086]

estrous cycle [A type of ovulation cycle, which occurs in most mammalian therian females, where the endometrium is resorbed if pregnancy does not occur. GO:0044849]

glomerular mesangial cell proliferation [The multiplication or reproduction of glomerular mesangial cells, resulting in the expansion of the population. GO:0072110]

interleukin-1-mediated signaling pathway [The series of molecular signals initiated by interleukin-1 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:0070498]

learning or memory [The acquisition and processing of information and/or the storage and retrieval of this information over time. GO:0007611]

locomotor rhythm [The rhythm of the locomotor activity of an organism during its 24 hour activity cycle. GO:0045475]

long-term memory [The memory process that deals with the storage, retrieval and modification of information a long time (typically weeks, months or years) after receiving that information. This type of memory is typically dependent on gene transcription regulated by second messenger activation. GO:0007616]

long-term synaptic potentiation [A process that modulates synaptic plasticity such that synapses are changed resulting in the increase in the rate, or frequency of synaptic transmission at the synapse. GO:0060291]

negative regulation of canonical Wnt signaling pathway [Any process that decreases the rate, frequency, or extent of the Wnt signaling pathway through beta-catenin, the series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell, followed by propagation of the signal via beta-catenin, and ending with a change in transcription of target genes. GO:0090090]

negative regulation of transcription by RNA polymerase II [Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II. GO:0000122]

obsolete regulation of transcription from RNA polymerase II promoter in response to hypoxia [Any process that modulates the frequency, rate or extent of transcription from an RNA polymerase II promoter as a result of a hypoxia stimulus. GO:0061418]

oligodendrocyte differentiation [The process in which a relatively unspecialized cell acquires the specialized features of an oligodendrocyte. An oligodendrocyte is a type of glial cell involved in myelinating the axons of neurons in the central nervous system. GO:0048709]

positive regulation of DNA-templated transcription [Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription. GO:0045893]

positive regulation of chemokine production [Any process that activates or increases the frequency, rate, or extent of chemokine production. GO:0032722]

positive regulation of gene expression [Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA). GO:0010628]

positive regulation of glomerular metanephric mesangial cell proliferation [Any process that increases the frequency, rate or extent of metanephric glomerular mesangial cell proliferation. GO:0072303]

positive regulation of hormone biosynthetic process [Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of hormones. GO:0046886]

positive regulation of interleukin-1 beta production [Any process that activates or increases the frequency, rate, or extent of interleukin-1 beta production. GO:0032731]

positive regulation of miRNA transcription [Any process that activates or increases the frequency, rate or extent of microRNA (miRNA) gene transcription. GO:1902895]

positive regulation of neuron apoptotic process [Any process that activates or increases the frequency, rate or extent of cell death of neurons by apoptotic process. GO:0043525]

positive regulation of post-translational protein modification [Any process that activates or increases the frequency, rate or extent of post-translational protein modification. GO:1901875]

positive regulation of smooth muscle cell migration [Any process that activates, maintains or increases the frequency, rate or extent of smooth muscle cell migration. GO:0014911]

positive regulation of smooth muscle cell proliferation [Any process that activates or increases the rate or extent of smooth muscle cell proliferation. GO:0048661]

positive regulation of transcription by RNA polymerase II [Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. GO:0045944]

regulation of DNA-templated transcription [Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription. GO:0006355]

regulation of apoptotic process [Any process that modulates the occurrence or rate of cell death by apoptotic process. This term should only be used when it is not possible to determine which phase or subtype of the apoptotic process is regulated by a gene product. Whenever detailed information is available, the more granular children terms should be used. GO:0042981]

regulation of long-term neuronal synaptic plasticity [A process that modulates long-term neuronal synaptic plasticity, the ability of neuronal synapses to change long-term as circumstances require. Long-term neuronal synaptic plasticity generally involves increase or decrease in actual synapse numbers. Note that the syntax of the definition of this term is different from the usual regulation syntax because it describes regulation of a trait rather than regulation of a process. GO:0048169]

regulation of neuron apoptotic process [Any process that modulates the occurrence or rate of cell death by apoptotic process in neurons. GO:0043523]

regulation of progesterone biosynthetic process [Any process that modulates the frequency, rate or extent of progesterone biosynthetic process. GO:2000182]

regulation of protein sumoylation [Any process that modulates the frequency, rate or extent of the addition of SUMO groups to a protein. GO:0033233]

regulation of transcription by RNA polymerase II [Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II. GO:0006357]

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 carbon monoxide [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 carbon monoxide (CO) stimulus. GO:0034465]

response to cocaine [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 cocaine stimulus. Cocaine is a crystalline alkaloid obtained from the leaves of the coca plant. GO:0042220]

response to electrical stimulus [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 electrical stimulus. GO:0051602]

response to ethanol [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 ethanol stimulus. GO:0045471]

response to follicle-stimulating hormone [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 follicle-stimulating hormone stimulus. GO:0032354]

response to glucose [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 glucose stimulus. GO:0009749]

response to gonadotropin [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 gonadotropin stimulus. GO:0034698]

response to hypoxia [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 stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level. Note that this term should not be confused with 'response to anoxia ; GO:0034059'. Note that in laboratory studies, hypoxia is typically studied at O2 concentrations ranging from 0.1 - 5%. GO:0001666]

response to insulin [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 insulin stimulus. Insulin is a polypeptide hormone produced by the islets of Langerhans of the pancreas in mammals, and by the homologous organs of other organisms. GO:0032868]

response to ischemia [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 inadequate blood supply. Ischemia always results in hypoxia; however, hypoxia can occur without ischemia. GO:0002931]

response to norepinephrine [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 norepinephrine stimulus. Norepinephrine is a catecholamine that has the formula C8H11NO3; it acts as a hormone, and as a neurotransmitter in most of the sympathetic nervous system. Note that epinephrine and norepinephrine are ligands for the same receptors, and there are multiple adrenergic receptors. GO:0071873]

response to nutrient levels [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 stimulus reflecting the presence, absence, or concentration of nutrients. GO:0031667]

response to xenobiotic stimulus [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 stimulus from a xenobiotic, a compound foreign to the organism exposed to it. It may be synthesized by another organism (like ampicillin) or it can be a synthetic chemical. GO:0009410]

skeletal muscle cell differentiation [The process in which a relatively unspecialized cell acquires specialized features of a skeletal muscle cell, a somatic cell located in skeletal muscle. GO:0035914]

MSigDB Signatures:

WP_NUCLEAR_RECEPTORS_META_PATHWAY: Nuclear receptors meta pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_NUCLEAR_RECEPTORS_META_PATHWAY.html]

WP_PRE_IMPLANTATION_EMBRYO: Pre implantation embryo [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_PRE_IMPLANTATION_EMBRYO.html]

KEGG_MEDICUS_REFERENCE_PRNP_PI3K_NOX2_SIGNALING_PATHWAY: Pathway Definition from KEGG: PRNP -> CAV -> FYN -> PI3K -> PRKCD -> NOX2 -> ERK -> CREB => EGR1 [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_MEDICUS_REFERENCE_PRNP_PI3K_NOX2_SIGNALING_PATHWAY.html]

WP_VEGFA_VEGFR2_SIGNALING: VEGFA VEGFR2 signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_VEGFA_VEGFR2_SIGNALING.html]

REACTOME_SIGNALING_BY_RECEPTOR_TYROSINE_KINASES: Signaling by Receptor Tyrosine Kinases [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SIGNALING_BY_RECEPTOR_TYROSINE_KINASES.html]

WP_INSULIN_SIGNALING: Insulin signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_INSULIN_SIGNALING.html]

REACTOME_INTRACELLULAR_SIGNALING_BY_SECOND_MESSENGERS: Intracellular signaling by second messengers [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INTRACELLULAR_SIGNALING_BY_SECOND_MESSENGERS.html]

REACTOME_NUCLEAR_EVENTS_KINASE_AND_TRANSCRIPTION_FACTOR_ACTIVATION: Nuclear Events (kinase and transcription factor activation) [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_NUCLEAR_EVENTS_KINASE_AND_TRANSCRIPTION_FACTOR_ACTIVATION.html]

WP_GASTRIN_SIGNALING_PATHWAY: Gastrin signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_GASTRIN_SIGNALING_PATHWAY.html]

REACTOME_INTERFERON_SIGNALING: Interferon Signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INTERFERON_SIGNALING.html]

WP_ONCOSTATIN_M_SIGNALING_PATHWAY: Oncostatin M signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_ONCOSTATIN_M_SIGNALING_PATHWAY.html]

7. Gene Descriptions

NCBI Gene Summary: The protein encoded by this gene belongs to the EGR family of C2H2-type zinc-finger proteins. It is a nuclear protein and functions as a transcriptional regulator. The products of target genes it activates are required for differentiation and mitogenesis. Studies suggest this is a cancer suppressor gene. [provided by RefSeq, Dec 2014]

GeneCards Summary: EGR1 (Early Growth Response 1) is a Protein Coding gene. Diseases associated with EGR1 include Ischemia and Monocytic Leukemia. Among its related pathways are PIP3 activates AKT signaling and Hepatocyte growth factor receptor signaling. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and transcription factor binding. An important paralog of this gene is EGR3.

UniProtKB/Swiss-Prot Summary: Transcriptional regulator [PMID: 20121949]. Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes. Binds double-stranded target DNA, irrespective of the cytosine methylation status [PMID: 25258363, PMID: 25999311]. Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia. Plays a role in the regulation of cell survival, proliferation and cell death. Activates expression of p53/TP53 and TGFB1, and thereby helps prevent tumor formation. Required for normal progress through mitosis and normal proliferation of hepatocytes after partial hepatectomy. Mediates responses to ischemia and hypoxia; regulates the expression of proteins such as IL1B and CXCL2 that are involved in inflammatory processes and development of tissue damage after ischemia. Regulates biosynthesis of luteinizing hormone (LHB) in the pituitary. Regulates the amplitude of the expression rhythms of clock genes: BMAL1, PER2 and NR1D1 in the liver via the activation of PER1 (clock repressor) transcription. Regulates the rhythmic expression of core-clock gene BMAL1 in the suprachiasmatic nucleus (SCN).

8. Cellular Location of Gene Product

General nuclear expression. Localized to the nucleoplasm. Predicted location: Intracellular [https://www.proteinatlas.org/ENSG00000120738/subcellular]

9. Mechanistic Information

Summary

In colon diseases and toxicities, EGR1 dysregulation occurs as a response to cellular stress, with its regulation of cell survival, proliferation, and death mechanisms being key [CS: 9]. For instance, in colon cancer, low EGR1 expression correlates with poor prognosis, while its overexpression hampers cancer cell proliferation, migration, and invasion [CS: 8]. This effect is partly due to EGR1's role in activating tumor suppressor genes like TGFbeta1, PTEN, p53, and fibronectin [CS: 7]. Specifically, EGR1-driven p53 activation instigates cell cycle arrest, thereby halting the proliferation of damaged cells and impeding cancer progression [CS: 8].

In inflammatory bowel diseases, EGR1 is upregulated in response to inflammatory triggers, such as TNF-alpha [CS: 8]. This upregulation enhances binding to promoters of genes like mPGES-1, which plays a role in inflammation and pain response [CS: 7]. Moreover, EGR1's regulation extends to the Na(+)/H(+) exchanger (NHE2), important in maintaining pH balance and cell volume in the intestine [CS: 6].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: low tissue specificity [https://www.proteinatlas.org/ENSG00000120738/tissue]

Cell type enchanced: basal prostatic cells, skeletal myocytes (cell type enhanced) [https://www.proteinatlas.org/ENSG00000120738/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: