TISIDB

Summary
Symbol	EGR1
Name	early growth response 1
Aliases	TIS8; G0S30; NGFI-A; KROX-24; ZIF-268; AT225; nerve growth factor-induced protein A; transcription factor ET ......
Chromosomal Location	5q23-q31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Nucleus Cytoplasm
Domain	PF11914 Domain of unknown function (DUF3432) PF11928 Domain of unknown function (DUF3446)
Function	Transcriptional regulator (PubMed:20121949). Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes (By similarity). Binds double-stranded target DNA, irrespective of the cytosine methylation status (PubMed:25258363, PubMed: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 (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0001655 urogenital system development GO:0001656 metanephros development GO:0001666 response to hypoxia GO:0001819 positive regulation of cytokine production GO:0001822 kidney development GO:0002521 leukocyte differentiation GO:0002931 response to ischemia GO:0006694 steroid biosynthetic process GO:0006700 C21-steroid hormone biosynthetic process GO:0006701 progesterone biosynthetic process GO:0007159 leukocyte cell-cell adhesion GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007517 muscle organ development GO:0007519 skeletal muscle tissue development GO:0008202 steroid metabolic process GO:0008207 C21-steroid hormone metabolic process GO:0009314 response to radiation GO:0009743 response to carbohydrate GO:0009746 response to hexose GO:0009749 response to glucose GO:0010212 response to ionizing radiation GO:0010332 response to gamma radiation GO:0010565 regulation of cellular ketone metabolic process GO:0010566 regulation of ketone biosynthetic process GO:0010817 regulation of hormone levels GO:0014706 striated muscle tissue development GO:0016055 Wnt signaling pathway GO:0016925 protein sumoylation GO:0018205 peptidyl-lysine modification GO:0019216 regulation of lipid metabolic process GO:0019218 regulation of steroid metabolic process GO:0030098 lymphocyte differentiation GO:0030111 regulation of Wnt signaling pathway GO:0030178 negative regulation of Wnt signaling pathway GO:0030217 T cell differentiation GO:0030509 BMP signaling pathway GO:0032350 regulation of hormone metabolic process GO:0032352 positive regulation of hormone metabolic process GO:0032602 chemokine production GO:0032611 interleukin-1 beta production GO:0032612 interleukin-1 production GO:0032642 regulation of chemokine production GO:0032651 regulation of interleukin-1 beta production GO:0032652 regulation of interleukin-1 production GO:0032722 positive regulation of chemokine production GO:0032731 positive regulation of interleukin-1 beta production GO:0032732 positive regulation of interleukin-1 production GO:0032835 glomerulus development GO:0032868 response to insulin GO:0033233 regulation of protein sumoylation GO:0034284 response to monosaccharide GO:0034340 response to type I interferon GO:0034754 cellular hormone metabolic process GO:0035914 skeletal muscle cell differentiation GO:0036293 response to decreased oxygen levels GO:0036294 cellular response to decreased oxygen levels GO:0042033 chemokine biosynthetic process GO:0042035 regulation of cytokine biosynthetic process GO:0042089 cytokine biosynthetic process GO:0042107 cytokine metabolic process GO:0042108 positive regulation of cytokine biosynthetic process GO:0042110 T cell activation GO:0042180 cellular ketone metabolic process GO:0042181 ketone biosynthetic process GO:0042222 interleukin-1 biosynthetic process GO:0042445 hormone metabolic process GO:0042446 hormone biosynthetic process GO:0042448 progesterone metabolic process GO:0042698 ovulation cycle GO:0043434 response to peptide hormone GO:0043618 regulation of transcription from RNA polymerase II promoter in response to stress GO:0043620 regulation of DNA-templated transcription in response to stress GO:0044283 small molecule biosynthetic process GO:0044849 estrous cycle GO:0045073 regulation of chemokine biosynthetic process GO:0045080 positive regulation of chemokine biosynthetic process GO:0045360 regulation of interleukin-1 biosynthetic process GO:0045362 positive regulation of interleukin-1 biosynthetic process GO:0046885 regulation of hormone biosynthetic process GO:0046886 positive regulation of hormone biosynthetic process GO:0046890 regulation of lipid biosynthetic process GO:0048511 rhythmic process GO:0050720 interleukin-1 beta biosynthetic process GO:0050722 regulation of interleukin-1 beta biosynthetic process GO:0050725 positive regulation of interleukin-1 beta biosynthetic process GO:0050755 chemokine metabolic process GO:0050810 regulation of steroid biosynthetic process GO:0060070 canonical Wnt signaling pathway GO:0060337 type I interferon signaling pathway GO:0060537 muscle tissue development GO:0060538 skeletal muscle organ development GO:0060828 regulation of canonical Wnt signaling pathway GO:0061418 regulation of transcription from RNA polymerase II promoter in response to hypoxia GO:0061437 renal system vasculature development GO:0061440 kidney vasculature development GO:0061448 connective tissue development GO:0070482 response to oxygen levels GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0070498 interleukin-1-mediated signaling pathway GO:0070555 response to interleukin-1 GO:0071214 cellular response to abiotic stimulus GO:0071347 cellular response to interleukin-1 GO:0071357 cellular response to type I interferon GO:0071417 cellular response to organonitrogen compound GO:0071453 cellular response to oxygen levels GO:0071456 cellular response to hypoxia GO:0071478 cellular response to radiation GO:0071479 cellular response to ionizing radiation GO:0071480 cellular response to gamma radiation GO:0071503 response to heparin GO:0071504 cellular response to heparin GO:0071505 response to mycophenolic acid GO:0071506 cellular response to mycophenolic acid GO:0071593 lymphocyte aggregation GO:0071772 response to BMP GO:0071773 cellular response to BMP stimulus GO:0072001 renal system development GO:0072006 nephron development GO:0072012 glomerulus vasculature development GO:0072109 glomerular mesangium development GO:0072110 glomerular mesangial cell proliferation GO:0072111 cell proliferation involved in kidney development GO:0072124 regulation of glomerular mesangial cell proliferation GO:0072126 positive regulation of glomerular mesangial cell proliferation GO:0072203 cell proliferation involved in metanephros development GO:0072210 metanephric nephron development GO:0072215 regulation of metanephros development GO:0072216 positive regulation of metanephros development GO:0072223 metanephric glomerular mesangium development GO:0072224 metanephric glomerulus development GO:0072239 metanephric glomerulus vasculature development GO:0072262 metanephric glomerular mesangial cell proliferation involved in metanephros development GO:0072298 regulation of metanephric glomerulus development GO:0072300 positive regulation of metanephric glomerulus development GO:0072301 regulation of metanephric glomerular mesangial cell proliferation GO:0072303 positive regulation of glomerular metanephric mesangial cell proliferation GO:0090090 negative regulation of canonical Wnt signaling pathway GO:0090183 regulation of kidney development GO:0090184 positive regulation of kidney development GO:0090192 regulation of glomerulus development GO:0090193 positive regulation of glomerulus development GO:0098758 response to interleukin-8 GO:0098759 cellular response to interleukin-8 GO:0198738 cell-cell signaling by wnt GO:1901342 regulation of vasculature development GO:1901652 response to peptide GO:1901722 regulation of cell proliferation involved in kidney development GO:1901724 positive regulation of cell proliferation involved in kidney development GO:1903320 regulation of protein modification by small protein conjugation or removal GO:1904018 positive regulation of vasculature development GO:2000182 regulation of progesterone biosynthetic process
Molecular Function	GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0003682 chromatin binding GO:0010385 double-stranded methylated DNA binding GO:0035035 histone acetyltransferase binding GO:0044729 hemi-methylated DNA-binding GO:1990841 promoter-specific chromatin binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-168256: Immune System R-HSA-913531: Interferon Signaling R-HSA-909733: Interferon alpha/beta signaling

Summary
Symbol	EGR1
Name	early growth response 1
Aliases	TIS8; G0S30; NGFI-A; KROX-24; ZIF-268; AT225; nerve growth factor-induced protein A; transcription factor ET ......
Chromosomal Location	5q23-q31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between EGR1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between EGR1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23312906	Glioma; Mesothelioma	Promote immunity	In two non epithelial cancers (glioma and mesothelioma), we found that the epigenetic regulation of the NY-ESO1 gene requires the sequential recruitment of the HDAC1-mSin3a-NCOR, Dnmt3b-HDAC1-Egr1 and Dnmt1-PCNA-UHRF1-G9a complexes.The NY-ESO1 gene is a cancer/testis antigen considered to be suitable target for the immunotherapy of human malignancies.

Summary
Symbol	EGR1
Name	early growth response 1
Aliases	TIS8; G0S30; NGFI-A; KROX-24; ZIF-268; AT225; nerve growth factor-induced protein A; transcription factor ET ......
Chromosomal Location	5q23-q31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of EGR1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	EGR1
Name	early growth response 1
Aliases	TIS8; G0S30; NGFI-A; KROX-24; ZIF-268; AT225; nerve growth factor-induced protein A; transcription factor ET ......
Chromosomal Location	5q23-q31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of EGR1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.234	0.705
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.3	0.615
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.559	0.746
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.394	0.656
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.213	0.948
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.613	0.889
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.258	0.643
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.649	0.696
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.283	0.867
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.767	0.579
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	2.423	0.182
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.586	0.00479

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of EGR1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	2.7	4.7	0.294
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	14.3	-14.3	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	0	7.4	0.096
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	16.7	-16.7	0.429
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	EGR1
Name	early growth response 1
Aliases	TIS8; G0S30; NGFI-A; KROX-24; ZIF-268; AT225; nerve growth factor-induced protein A; transcription factor ET ......
Chromosomal Location	5q23-q31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of EGR1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	EGR1
Name	early growth response 1
Aliases	TIS8; G0S30; NGFI-A; KROX-24; ZIF-268; AT225; nerve growth factor-induced protein A; transcription factor ET ......
Chromosomal Location	5q23-q31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of EGR1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by EGR1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	EGR1
Name	early growth response 1
Aliases	TIS8; G0S30; NGFI-A; KROX-24; ZIF-268; AT225; nerve growth factor-induced protein A; transcription factor ET ......
Chromosomal Location	5q23-q31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of EGR1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	EGR1
Name	early growth response 1
Aliases	TIS8; G0S30; NGFI-A; KROX-24; ZIF-268; AT225; nerve growth factor-induced protein A; transcription factor ET ......
Chromosomal Location	5q23-q31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of EGR1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	EGR1
Name	early growth response 1
Aliases	TIS8; G0S30; NGFI-A; KROX-24; ZIF-268; AT225; nerve growth factor-induced protein A; transcription factor ET ......
Chromosomal Location	5q23-q31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between EGR1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	EGR1
Name	early growth response 1
Aliases	TIS8; G0S30; NGFI-A; KROX-24; ZIF-268; AT225; nerve growth factor-induced protein A; transcription factor ET ......
Chromosomal Location	5q23-q31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting EGR1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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