Browse IRF4

Summary
SymbolIRF4
Nameinterferon regulatory factor 4
Aliases LSIRF; NF-EM5; SHEP8; lymphocyte-specific interferon regulatory factor; multiple myeloma oncogene 1; IRF-4
Chromosomal Location6p25-p23
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
 
Subcellular Location Nucleus.
Domain PF00605 Interferon regulatory factor transcription factor
PF10401 Interferon-regulatory factor 3
Function

Transcriptional activator. Binds to the interferon-stimulated response element (ISRE) of the MHC class I promoter. Binds the immunoglobulin lambda light chain enhancer, together with PU.1. Probably plays a role in ISRE-targeted signal transduction mechanisms specific to lymphoid cells. Involved in CD8(+) dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF4 and activation of genes (By similarity).

> Gene Ontology
 
Biological Process GO:0001562 response to protozoan
GO:0001773 myeloid dendritic cell activation
GO:0001819 positive regulation of cytokine production
GO:0002218 activation of innate immune response
GO:0002221 pattern recognition receptor signaling pathway
GO:0002224 toll-like receptor signaling pathway
GO:0002250 adaptive immune response
GO:0002263 cell activation involved in immune response
GO:0002274 myeloid leukocyte activation
GO:0002285 lymphocyte activation involved in immune response
GO:0002286 T cell activation involved in immune response
GO:0002287 alpha-beta T cell activation involved in immune response
GO:0002292 T cell differentiation involved in immune response
GO:0002293 alpha-beta T cell differentiation involved in immune response
GO:0002294 CD4-positive, alpha-beta T cell differentiation involved in immune response
GO:0002295 T-helper cell lineage commitment
GO:0002360 T cell lineage commitment
GO:0002363 alpha-beta T cell lineage commitment
GO:0002366 leukocyte activation involved in immune response
GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002521 leukocyte differentiation
GO:0002573 myeloid leukocyte differentiation
GO:0002683 negative regulation of immune system process
GO:0002694 regulation of leukocyte activation
GO:0002697 regulation of immune effector process
GO:0002757 immune response-activating signal transduction
GO:0002758 innate immune response-activating signal transduction
GO:0002764 immune response-regulating signaling pathway
GO:0006473 protein acetylation
GO:0006475 internal protein amino acid acetylation
GO:0006479 protein methylation
GO:0007159 leukocyte cell-cell adhesion
GO:0008213 protein alkylation
GO:0016570 histone modification
GO:0016573 histone acetylation
GO:0018022 peptidyl-lysine methylation
GO:0018205 peptidyl-lysine modification
GO:0018393 internal peptidyl-lysine acetylation
GO:0018394 peptidyl-lysine acetylation
GO:0022407 regulation of cell-cell adhesion
GO:0030098 lymphocyte differentiation
GO:0030099 myeloid cell differentiation
GO:0030217 T cell differentiation
GO:0031349 positive regulation of defense response
GO:0032259 methylation
GO:0032613 interleukin-10 production
GO:0032616 interleukin-13 production
GO:0032623 interleukin-2 production
GO:0032633 interleukin-4 production
GO:0032653 regulation of interleukin-10 production
GO:0032656 regulation of interleukin-13 production
GO:0032663 regulation of interleukin-2 production
GO:0032673 regulation of interleukin-4 production
GO:0032733 positive regulation of interleukin-10 production
GO:0032736 positive regulation of interleukin-13 production
GO:0032743 positive regulation of interleukin-2 production
GO:0032753 positive regulation of interleukin-4 production
GO:0034121 regulation of toll-like receptor signaling pathway
GO:0034122 negative regulation of toll-like receptor signaling pathway
GO:0034340 response to type I interferon
GO:0034341 response to interferon-gamma
GO:0035710 CD4-positive, alpha-beta T cell activation
GO:0042035 regulation of cytokine biosynthetic process
GO:0042089 cytokine biosynthetic process
GO:0042091 interleukin-10 biosynthetic process
GO:0042093 T-helper cell differentiation
GO:0042094 interleukin-2 biosynthetic process
GO:0042097 interleukin-4 biosynthetic process
GO:0042107 cytokine metabolic process
GO:0042108 positive regulation of cytokine biosynthetic process
GO:0042110 T cell activation
GO:0042231 interleukin-13 biosynthetic process
GO:0042832 defense response to protozoan
GO:0043011 myeloid dendritic cell differentiation
GO:0043367 CD4-positive, alpha-beta T cell differentiation
GO:0043368 positive T cell selection
GO:0043369 CD4-positive or CD8-positive, alpha-beta T cell lineage commitment
GO:0043370 regulation of CD4-positive, alpha-beta T cell differentiation
GO:0043373 CD4-positive, alpha-beta T cell lineage commitment
GO:0043388 positive regulation of DNA binding
GO:0043414 macromolecule methylation
GO:0043543 protein acylation
GO:0043966 histone H3 acetylation
GO:0043967 histone H4 acetylation
GO:0045058 T cell selection
GO:0045074 regulation of interleukin-10 biosynthetic process
GO:0045076 regulation of interleukin-2 biosynthetic process
GO:0045082 positive regulation of interleukin-10 biosynthetic process
GO:0045086 positive regulation of interleukin-2 biosynthetic process
GO:0045088 regulation of innate immune response
GO:0045089 positive regulation of innate immune response
GO:0045165 cell fate commitment
GO:0045366 regulation of interleukin-13 biosynthetic process
GO:0045368 positive regulation of interleukin-13 biosynthetic process
GO:0045402 regulation of interleukin-4 biosynthetic process
GO:0045404 positive regulation of interleukin-4 biosynthetic process
GO:0045580 regulation of T cell differentiation
GO:0045619 regulation of lymphocyte differentiation
GO:0045622 regulation of T-helper cell differentiation
GO:0046631 alpha-beta T cell activation
GO:0046632 alpha-beta T cell differentiation
GO:0046634 regulation of alpha-beta T cell activation
GO:0046637 regulation of alpha-beta T cell differentiation
GO:0050863 regulation of T cell activation
GO:0050865 regulation of cell activation
GO:0051098 regulation of binding
GO:0051099 positive regulation of binding
GO:0051101 regulation of DNA binding
GO:0051249 regulation of lymphocyte activation
GO:0060333 interferon-gamma-mediated signaling pathway
GO:0060337 type I interferon signaling pathway
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0071346 cellular response to interferon-gamma
GO:0071357 cellular response to type I interferon
GO:0071593 lymphocyte aggregation
GO:0072538 T-helper 17 type immune response
GO:0072539 T-helper 17 cell differentiation
GO:0072540 T-helper 17 cell lineage commitment
GO:0097028 dendritic cell differentiation
GO:0098542 defense response to other organism
GO:1902105 regulation of leukocyte differentiation
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903706 regulation of hemopoiesis
GO:2000514 regulation of CD4-positive, alpha-beta T cell activation
Molecular Function GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0000987 core promoter proximal region sequence-specific DNA binding
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0001159 core promoter proximal region DNA binding
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0008134 transcription factor binding
GO:0008168 methyltransferase activity
GO:0008170 N-methyltransferase activity
GO:0008276 protein methyltransferase activity
GO:0008757 S-adenosylmethionine-dependent methyltransferase activity
GO:0016278 lysine N-methyltransferase activity
GO:0016279 protein-lysine N-methyltransferase activity
GO:0016741 transferase activity, transferring one-carbon groups
Cellular Component GO:0000785 chromatin
GO:0000786 nucleosome
GO:0000788 nuclear nucleosome
GO:0000790 nuclear chromatin
GO:0032993 protein-DNA complex
GO:0044454 nuclear chromosome part
GO:0044815 DNA packaging complex
> KEGG and Reactome Pathway
 
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
R-HSA-877300: Interferon gamma signaling
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-449147: Signaling by Interleukins
Summary
SymbolIRF4
Nameinterferon regulatory factor 4
Aliases LSIRF; NF-EM5; SHEP8; lymphocyte-specific interferon regulatory factor; multiple myeloma oncogene 1; IRF-4
Chromosomal Location6p25-p23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between IRF4 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
 
  Literatures describing the relation between IRF4 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28494239Endemic Burkitt LymphomaInhibit immunityOur systematic approach uncovered key mechanisms by which EBV oncoproteins activate the PI3K/AKT pathway and evade tumor suppressor responses. LMP1-induced cFLIP was found to be critical for LCL defense against TNFα-mediated programmed cell death, whereas EBV-induced BATF/IRF4 were critical for BIM suppression and MYC induction in LCLs.
18568025Plasma Cell MyelomaPromote immunityThe transcription factor IRF4 (interferon regulatory factor 4) is required during an immune response for lymphocyte activation and the generation of immunoglobulin-secreting plasma cells.
20585039B Lymphoblastic Leukemia/LymphomaPromote immunity (alone); Inhibit immunity (combine with IRF8)Cooperation between deficiencies of IRF-4 and IRF-8 promotes both myeloid and lymphoid tumorigenesis. Although these results demonstrate, for the first time, that IRF-4 can function as tumor suppressor in myeloid cells, interestingly, all mice deficient in both IRF-4 and IRF-8 eventually develop and die of a B-lymphoblastic leukemia/lymphoma.
18713947B Acute Lymphoblastic LeukemiaPromote immunityIRF-4 functions as a tumor suppressor in early B-cell development. We further found that IRF-4 deficiency enhances BCR/ABL transformation of B-lymphoid progenitors in vitro and accelerates disease progression of BCR/ABL-induced acute B-lymphoblastic leukemia (B-ALL) in mice, whereas forced expression of IRF-4 potently suppresses BCR/ABL transformation of B-lymphoid progenitors in vitro and BCR/ABL-induced B-ALL in vivo. Further analysis showed that IRF-4 inhibits growth of BCR/ABL+ B lymphoblasts primarily through negative regulation of cell-cycle progression.
Summary
SymbolIRF4
Nameinterferon regulatory factor 4
Aliases LSIRF; NF-EM5; SHEP8; lymphocyte-specific interferon regulatory factor; multiple myeloma oncogene 1; IRF-4
Chromosomal Location6p25-p23
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
  Statistical results of IRF4 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolIRF4
Nameinterferon regulatory factor 4
Aliases LSIRF; NF-EM5; SHEP8; lymphocyte-specific interferon regulatory factor; multiple myeloma oncogene 1; IRF-4
Chromosomal Location6p25-p23
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
 
Points in the above scatter plot represent the expression difference of IRF4 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.610.379
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)651.2960.507
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.1130.938
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.0020.997
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.3410.799
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.4360.815
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.4220.428
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.7350.675
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.0110.996
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.1210.0783
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.8170.336
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0220.934
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of IRF4 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277302.7-2.71
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 01407.1-7.11
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.509.50.492
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)86250250.473
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolIRF4
Nameinterferon regulatory factor 4
Aliases LSIRF; NF-EM5; SHEP8; lymphocyte-specific interferon regulatory factor; multiple myeloma oncogene 1; IRF-4
Chromosomal Location6p25-p23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IRF4. 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
 
Summary
SymbolIRF4
Nameinterferon regulatory factor 4
Aliases LSIRF; NF-EM5; SHEP8; lymphocyte-specific interferon regulatory factor; multiple myeloma oncogene 1; IRF-4
Chromosomal Location6p25-p23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IRF4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IRF4.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolIRF4
Nameinterferon regulatory factor 4
Aliases LSIRF; NF-EM5; SHEP8; lymphocyte-specific interferon regulatory factor; multiple myeloma oncogene 1; IRF-4
Chromosomal Location6p25-p23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IRF4. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolIRF4
Nameinterferon regulatory factor 4
Aliases LSIRF; NF-EM5; SHEP8; lymphocyte-specific interferon regulatory factor; multiple myeloma oncogene 1; IRF-4
Chromosomal Location6p25-p23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of IRF4 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolIRF4
Nameinterferon regulatory factor 4
Aliases LSIRF; NF-EM5; SHEP8; lymphocyte-specific interferon regulatory factor; multiple myeloma oncogene 1; IRF-4
Chromosomal Location6p25-p23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between IRF4 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolIRF4
Nameinterferon regulatory factor 4
Aliases LSIRF; NF-EM5; SHEP8; lymphocyte-specific interferon regulatory factor; multiple myeloma oncogene 1; IRF-4
Chromosomal Location6p25-p23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting IRF4 collected from DrugBank database.
> Drugs from DrugBank database
 

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