IRF4

Interferon regulatory factor 4
PDB rendering based on 2dll.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2DLL​
Identifiers
Symbols	IRF4 ; LSIRF; MUM1; NF-EM5; SHEP8
External IDs	OMIM: 601900 MGI: 1096873 HomoloGene: 1842 GeneCards: IRF4 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • transcription factor activity, sequence-specific DNA binding • protein binding • transcription factor binding • protein-lysine N-methyltransferase activity • sequence-specific DNA binding Cellular component • nuclear nucleosome • nucleus • nucleoplasm • cytoplasm • cytosol • membrane Biological process • transcription from RNA polymerase II promoter • peptidyl-lysine methylation • cytokine-mediated signaling pathway • negative regulation of toll-like receptor signaling pathway • T cell activation • defense response to protozoan • myeloid dendritic cell differentiation • positive regulation of DNA binding • histone H3 acetylation • histone H4 acetylation • positive regulation of interleukin-10 biosynthetic process • positive regulation of interleukin-2 biosynthetic process • positive regulation of interleukin-13 biosynthetic process • positive regulation of interleukin-4 biosynthetic process • regulation of T-helper cell differentiation • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • interferon-gamma-mediated signaling pathway • type I interferon signaling pathway • T-helper 17 cell lineage commitment Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3662	16364
Ensembl	ENSG00000137265	ENSMUSG00000021356
UniProt	Q15306	Q64287
RefSeq (mRNA)	NM_001195286	NM_013674
RefSeq (protein)	NP_001182215	NP_038702
Location (UCSC)	Chr 6: 0.39 – 0.41 Mb	Chr 13: 30.75 – 30.77 Mb
PubMed search

Interferon regulatory factor 4 also known as MUM1 is a protein that in humans is encoded by the IRF4 gene,^[1][2][3] located at 6p25-p23.

The MUM1 symbol is polysemous; although it is an older synonym for IRF4 (HGNC:6119), it is also the current HGNC official symbol for melanoma associated antigen (mutated) 1 (HGNC:29641; located at 19p13.3).

Clinical significance

In melanocytic cells the IRF4 gene may be regulated by MITF.^[4] IRF4 is a transcription factor that has been implicated in acute leukemia.^[5] This gene is strongly associated with pigmentation: sensitivity of skin to sun exposure, freckles, blue eyes, and brown hair color.^[6] A variant has been implicated in greying of hair.^[7]

Interactions

IRF4 has been shown to interact with:

• BCL6,^[8]
• NFATC2,^[9]
• SPI1,^[10][11] and
• STAT6.^[8]

See also

• Interferon regulatory factors

References

1. Grossman A, Mittrücker HW, Nicholl J, Suzuki A, Chung S, Antonio L, Suggs S, Sutherland GR, Siderovski DP, Mak TW (Feb 1997). "Cloning of human lymphocyte-specific interferon regulatory factor (hLSIRF/hIRF4) and mapping of the gene to 6p23-p25". Genomics 37 (2): 229–33. doi:10.1006/geno.1996.0547. PMID 8921401.
2. Xu D, Zhao L, Del Valle L, Miklossy J, Zhang L (Jun 2008). "Interferon regulatory factor 4 is involved in Epstein-Barr virus-mediated transformation of human B lymphocytes". J Virol 82 (13): 6251–8. doi:10.1128/JVI.00163-08. PMC 2447047. PMID 18417578.
3. "Entrez Gene: IRF4 interferon regulatory factor 4".
4. Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
5. Adamaki M, Lambrou GI, Athanasiadou A, Tzanoudaki M, Vlahopoulos S, Moschovi M (2013). "Implication of IRF4 aberrant gene expression in the acute leukemias of childhood". PLoS ONE 8 (8): e72326. doi:10.1371/journal.pone.0072326. PMC 3744475. PMID 23977280.
6. Praetorius C, Grill C, Stacey SN, Metcalf AM, Gorkin DU, Robinson KC, et al. (November 2013). "A Polymorphism in IRF4 Affects Human Pigmentation through a Tyrosinase-Dependent MITF/TFAP2A Pathway". Cell 155 (5): 1022–33. doi:10.1016/j.cell.2013.10.022. PMID 24267888.
7. Adhikari K, Fontanil T, Cal S, Mendoza-Revilla J, Fuentes-Guajardo M, Chacón-Duque JC, et al. (2016). "A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features". Nature Communications 7: 10815. doi:10.1038/ncomms10815. PMID 26926045. Lay summary – BBC News.
8. Gupta S, Jiang M, Anthony A, Pernis AB (December 1999). "Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4". J. Exp. Med. 190 (12): 1837–48. doi:10.1084/jem.190.12.1837. PMC 2195723. PMID 10601358.
9. Rengarajan J, Mowen KA, McBride KD, Smith ED, Singh H, Glimcher LH (April 2002). "Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression". J. Exp. Med. 195 (8): 1003–12. doi:10.1084/jem.20011128. PMC 2193700. PMID 11956291.
10. Brass AL, Zhu AQ, Singh H (February 1999). "Assembly requirements of PU.1-Pip (IRF-4) activator complexes: inhibiting function in vivo using fused dimers". EMBO J. 18 (4): 977–91. doi:10.1093/emboj/18.4.977. PMC 1171190. PMID 10022840.
11. Escalante CR, Shen L, Escalante MC, Brass AL, Edwards TA, Singh H, Aggarwal AK (July 2002). "Crystallization and characterization of PU.1/IRF-4/DNA ternary complex". J. Struct. Biol. 139 (1): 55–9. doi:10.1016/S1047-8477(02)00514-2. PMID 12372320.

Further reading

• Mamane Y, Sharma S, Grandvaux N, Hernandez E, Hiscott J (2002). "IRF-4 activities in HTLV-I-induced T cell leukemogenesis". J. Interferon Cytokine Res. 22 (1): 135–43. doi:10.1089/107999002753452746. PMID 11846984.
• Yamagata T, Nishida J, Tanaka S, Sakai R, Mitani K, Yoshida M, Taniguchi T, Yazaki Y, Hirai H (1996). "A novel interferon regulatory factor family transcription factor, ICSAT/Pip/LSIRF, that negatively regulates the activity of interferon-regulated genes". Mol. Cell. Biol. 16 (4): 1283–94. PMC 231112. PMID 8657101.
• Iida S, Rao PH, Butler M, Corradini P, Boccadoro M, Klein B, Chaganti RS, Dalla-Favera R (1997). "Deregulation of MUM1/IRF4 by chromosomal translocation in multiple myeloma". Nat. Genet. 17 (2): 226–30. doi:10.1038/ng1097-226. PMID 9326949.
• Brass AL, Zhu AQ, Singh H (1999). "Assembly requirements of PU.1-Pip (IRF-4) activator complexes: inhibiting function in vivo using fused dimers". EMBO J. 18 (4): 977–91. doi:10.1093/emboj/18.4.977. PMC 1171190. PMID 10022840.
• Rao S, Matsumura A, Yoon J, Simon MC (1999). "SPI-B activates transcription via a unique proline, serine, and threonine domain and exhibits DNA binding affinity differences from PU.1". J. Biol. Chem. 274 (16): 11115–24. doi:10.1074/jbc.274.16.11115. PMID 10196196.
• Marecki S, Atchison ML, Fenton MJ (1999). "Differential expression and distinct functions of IFN regulatory factor 4 and IFN consensus sequence binding protein in macrophages". J. Immunol. 163 (5): 2713–22. PMID 10453013.
• Gupta S, Jiang M, Anthony A, Pernis AB (2000). "Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4". J. Exp. Med. 190 (12): 1837–48. doi:10.1084/jem.190.12.1837. PMC 2195723. PMID 10601358.
• Mamane Y, Sharma S, Petropoulos L, Lin R, Hiscott J (2000). "Posttranslational regulation of IRF-4 activity by the immunophilin FKBP52". Immunity 12 (2): 129–40. doi:10.1016/S1074-7613(00)80166-1. PMID 10714679.
• Gupta S, Anthony A, Pernis AB (2001). "Stage-specific modulation of IFN-regulatory factor 4 function by Krüppel-type zinc finger proteins". J. Immunol. 166 (10): 6104–11. doi:10.4049/jimmunol.166.10.6104. PMID 11342629.
• Imaizumi Y, Kohno T, Yamada Y, Ikeda S, Tanaka Y, Tomonaga M, Matsuyama T (2002). "Possible involvement of interferon regulatory factor 4 (IRF4) in a clinical subtype of adult T-cell leukemia". Jpn. J. Cancer Res. 92 (12): 1284–92. doi:10.1111/j.1349-7006.2001.tb02151.x. PMID 11749693.
• Rengarajan J, Mowen KA, McBride KD, Smith ED, Singh H, Glimcher LH (2002). "Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression". J. Exp. Med. 195 (8): 1003–12. doi:10.1084/jem.20011128. PMC 2193700. PMID 11956291.
• Sharma S, Grandvaux N, Mamane Y, Genin P, Azimi N, Waldmann T, Hiscott J (2002). "Regulation of IFN regulatory factor 4 expression in human T cell leukemia virus-I-transformed T cells". J. Immunol. 169 (6): 3120–30. doi:10.4049/jimmunol.169.6.3120. PMID 12218129.
• Escalante CR, Shen L, Escalante MC, Brass AL, Edwards TA, Singh H, Aggarwal AK (2003). "Crystallization and characterization of PU.1/IRF-4/DNA ternary complex". J. Struct. Biol. 139 (1): 55–9. doi:10.1016/S1047-8477(02)00514-2. PMID 12372320.
• Hu CM, Jang SY, Fanzo JC, Pernis AB (2003). "Modulation of T cell cytokine production by interferon regulatory factor-4". J. Biol. Chem. 277 (51): 49238–46. doi:10.1074/jbc.M205895200. PMID 12374808.
• Fanzo JC, Hu CM, Jang SY, Pernis AB (2003). "Regulation of lymphocyte apoptosis by interferon regulatory factor 4 (IRF-4)". J. Exp. Med. 197 (3): 303–14. doi:10.1084/jem.20020717. PMC 2193834. PMID 12566414.
• O'Reilly D, Quinn CM, El-Shanawany T, Gordon S, Greaves DR (2003). "Multiple Ets factors and interferon regulatory factor-4 modulate CD68 expression in a cell type-specific manner". J. Biol. Chem. 278 (24): 21909–19. doi:10.1074/jbc.M212150200. PMID 12676954.
• Sundram U, Harvell JD, Rouse RV, Natkunam Y (2004). "Expression of the B-cell proliferation marker MUM1 by melanocytic lesions and comparison with S100, gp100 (HMB45), and MelanA". Mod. Pathol. 16 (8): 802–10. doi:10.1097/01.MP.0000081726.49886.CF. PMID 12920225.

External links

• FactorBook IRF4
• IRF4 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.