IRF4

Interferon regulatory factor 4 also known as MUM1 is a protein that in humans is encoded by the IRF4 gene,[5][6][7] located at 6p25-p23.

IRF4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2DLL
Identifiers
Aliases	IRF4, LSIRF, MUM1, NF-EM5, SHEP8, interferon regulatory factor 4
External IDs	OMIM: 601900 MGI: 1096873 HomoloGene: 1842 GeneCards: IRF4
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p25.3 Start 391,752 bp[1] End 411,443 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13|13 A3.2 Start 30,749,226 bp[2] End 30,766,976 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • sequence-specific DNA binding • DNA binding • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • transcription factor binding • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • protein-lysine N-methyltransferase activity • GO:0001948 protein binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component • nuclear nucleosome • cytosol • membrane • nucleoplasm • cell nucleus Biological process • positive regulation of interleukin-13 biosynthetic process • regulation of transcription, DNA-templated • interferon-gamma-mediated signaling pathway • regulation of T-helper cell differentiation • myeloid dendritic cell differentiation • transcription, DNA-templated • T-helper 17 cell lineage commitment • positive regulation of interleukin-2 biosynthetic process • positive regulation of transcription, DNA-templated • peptidyl-lysine methylation • negative regulation of toll-like receptor signaling pathway • positive regulation of interleukin-10 biosynthetic process • type I interferon signaling pathway • histone H3 acetylation • histone H4 acetylation • positive regulation of DNA binding • T cell activation • positive regulation of interleukin-4 biosynthetic process • positive regulation of transcription from RNA polymerase II promoter • defense response to protozoan • protein methylation • transcription from RNA polymerase II promoter • cytokine-mediated signaling pathway • positive regulation of cold-induced thermogenesis • immune system process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3662	16364
Ensembl	ENSG00000137265	ENSMUSG00000021356
UniProt	Q15306	Q64287
RefSeq (mRNA)	NM_001195286 NM_002460	NM_013674 NM_001347508
RefSeq (protein)	NP_001182215 NP_002451	NP_001334437 NP_038702
Location (UCSC)	Chr 6: 0.39 – 0.41 Mb	Chr 13: 30.75 – 30.77 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[8] IRF4 is a transcription factor that has been implicated in acute leukemia.[9] This gene is strongly associated with pigmentation: sensitivity of skin to sun exposure, freckles, blue eyes, and brown hair color.[10] A variant has been implicated in greying of hair.[11]

The World Health Organization (2016) provisionally defined large B-cell lymphoma with IRF4 rearrangement as a rare indolent large B-cell lymphoma of children and adolescents. This indolent lymphoma mimics, and must be distinguished from, pediatric-type follicular lymphoma.[12] The hallmark of large B-cell lymphoma with IRF4 rearrangement is the overexpression of the IRF4 gene by the disease's malignant cells. This overexpression is forced by the acquisition in these cells of a translocation of IRF4 from its site on the short (i.e. p) arm of chromosome 6 at position 25.3[13] to a site near the IGH@ immunoglobulin heavy locus on the long (i.e. q) arm of chromosome 14 at position 32.33[14][15]

Interactions

IRF4 has been shown to interact with:

• BCL6,[16]
• NFATC2,[17]
• SPI1,[18][19] and
• STAT6.[16]

See also

• Interferon regulatory factors

References

1. GRCh38: Ensembl release 89: ENSG00000137265 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021356 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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.
7. "Entrez Gene: IRF4 interferon regulatory factor 4".
8. 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.
9. 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.
10. 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. PMC 3873608. PMID 24267888.
11. 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. PMC 4773514. PMID 26926045. Lay summary – BBC News.
12. Lynch RC, Gratzinger D, Advani RH (July 2017). "Clinical Impact of the 2016 Update to the WHO Lymphoma Classification". Current Treatment Options in Oncology. 18 (7): 45. doi:10.1007/s11864-017-0483-z. PMID 28670664.
13. https://www.ncbi.nlm.nih.gov/gene/3662
14. https://www.ncbi.nlm.nih.gov/gene/3492
15. Woessmann W, Quintanilla-Martinez L (June 2019). "Rare mature B-cell lymphomas in children and adolescents". Hematological Oncology. 37 Suppl 1: 53–61. doi:10.1002/hon.2585. PMID 31187530.
16. 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.
17. 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.
18. 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.
19. 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. doi:10.1128/MCB.16.4.1283. 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. PMC 5926682. 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.