Gene Symbol: ELK4
Description: ELK4, ETS transcription factor
Alias: SAP1, ETS domain-containing protein Elk-4, ELK4, ETS-domain protein (SRF accessory protein 1), SAP-1, serum response factor accessory protein 1
Species: human
Products:     ELK4

Top Publications

  1. Makkonen H, Jaaskelainen T, Pitkänen Arsiola T, Rytinki M, Waltering K, Matto M, et al. Identification of ETS-like transcription factor 4 as a novel androgen receptor target in prostate cancer cells. Oncogene. 2008;27:4865-76 pubmed publisher
    ..We have characterized E twenty-six-like transcription factor 4 (ELK4) (also known as serum response factor accessory protein 1) as a novel AR target in human prostate cancer cells...
  2. Zhang W, Li Y, Lin J, Abduryim A, Zhao J. Cariogenicity of Candida albicans of distinct genotypes among 3-5-year-old Uygur children in Kashgar, China- a case-control study. BMC Oral Health. 2018;18:203 pubmed publisher
    ..Moreover, secreted aspartic protease (Sap) activity and SAP1-5 transcriptional levels were compared in the ECC and caries-free (CF) groups of Uygur children. C...
  3. Rapala Kozik M, Bocheńska O, Zawrotniak M, Wolak N, Trebacz G, Gogol M, et al. Inactivation of the antifungal and immunomodulatory properties of human cathelicidin LL-37 by aspartic proteases produced by the pathogenic yeast Candida albicans. Infect Immun. 2015;83:2518-30 pubmed publisher
    ..albicans uses SAPs to effectively degrade LL-37. LL-37 is cleaved into multiple products by SAP1 to -4, SAP8, and SAP9, and this proteolytic processing is correlated with the gradual decrease in the antifungal ..
  4. Wenwen S, Liuping Z, Xiaoyan L, Lei F, Sun S. The synergistic antifungal effects of sodium phenylbutyrate combined with azoles against Candida albicans via regulating Ras/cAMP/PKA signalling pathway and virulence. Can J Microbiol. 2018;: pubmed publisher
    ..treatment decreased the extracellular phospholipase activities and the expression of aspartyl proteinase genes (SAP1-SAP3)...
  5. Jørgensen M, Ekundayo B, Zaratiegui M, Skriver K, Thon G, Schalch T. Structure of the replication regulator Sap1 reveals functionally important interfaces. Sci Rep. 2018;8:10930 pubmed publisher
    ..order to shed light on this process we carried out structural investigations on the essential fission yeast protein Sap1. Sap1 was identified as a protein involved in mating-type switching in Schizosaccharomyces pombe, and has been ..
  6. Du J, Wang X, Luo H, Wang Y, Liu X, Zhou X. Epidemiological investigation of non-albicans Candida species recovered from mycotic mastitis of cows in Yinchuan, Ningxia of China. BMC Vet Res. 2018;14:251 pubmed publisher
    ..Molecularly, all of the C. parapsilosis isolates carried eight virulence-related genes, FKS1, FKS2, FKS3, SAP1, SAP2, CDR1, ERG11 and MDR1. All of the C...
  7. Belmadani A, Semlali A, Rouabhia M. Dermaseptin-S1 decreases Candida albicans growth, biofilm formation and the expression of hyphal wall protein 1 and aspartic protease genes. J Appl Microbiol. 2018;125:72-83 pubmed publisher
    ..albicans growth, transition and biofilm formation may occur through gene modulation, as the expression of HWP1, SAP1, SAP2, SAP3, SAP9 and SAP10 genes involved in C. albicans pathogenesis were all downregulated when C...
  8. Kozik A, Gogol M, Bocheńska O, Karkowska Kuleta J, Wolak N, Kamysz W, et al. Kinin release from human kininogen by 10 aspartic proteases produced by pathogenic yeast Candida albicans. BMC Microbiol. 2015;15:60 pubmed publisher
    ..b>Sap1-6 and 8 produced a biologically active kinin-Met-Lys-bradykinin-and Sap3 was exceptional in terms of the kinin-..
  9. Maurice D, Costello P, Sargent M, Treisman R. ERK Signaling Controls Innate-like CD8+ T Cell Differentiation via the ELK4 (SAP-1) and ELK1 Transcription Factors. J Immunol. 2018;201:1681-1691 pubmed publisher
    ..The Ets transcription factor ELK4 (SAP-1), an ERK-regulated cofactor of the SRF transcription factor, plays an important role in positive selection ..

More Information


  1. Bestman J, Huang L, Lee Osbourne J, Cheung P, Cline H. An in vivo screen to identify candidate neurogenic genes in the developing Xenopus visual system. Dev Biol. 2015;408:269-91 pubmed publisher
    ..were tagged as differentially expressed and validated by the in vivo imaging screen include: actn1, arl9, eif3a, elk4, ephb1, fmr1-a, fxr1-1, fbxw7, fgf2, gstp1, hat1, hspa5, lsm6, mecp2, mmp9, and prkaca...
  2. Willoughby J, Costello P, Nicolas R, Robinson N, Stamp G, Powrie F, et al. Raf signaling but not the ERK effector SAP-1 is required for regulatory T cell development. J Immunol. 2007;179:6836-44 pubmed
  3. Weinl C, Wasylyk C, Garcia Garrido M, Sothilingam V, Beck S, Riehle H, et al. Elk3 deficiency causes transient impairment in post-natal retinal vascular development and formation of tortuous arteries in adult murine retinae. PLoS ONE. 2014;9:e107048 pubmed publisher
    ..Myocardin-Related Transcription Factors MRTF-A and -B, but not the Ternary Complex Factors (TCFs) Elk1 and Elk4. The role of the third TCF, Elk3, remained unknown...
  4. Gu W, Guo D, Zhang L, Xu D, Sun S. The Synergistic Effect of Azoles and Fluoxetine against Resistant Candida albicans Strains Is Attributed to Attenuating Fungal Virulence. Antimicrob Agents Chemother. 2016;60:6179-88 pubmed publisher
    ..study, we observed that fluconazole plus fluoxetine caused downregulation of the gene expression levels of SAP1 to SAP4 and weakened the extracellular phospholipase activities of resistant C...
  5. Kublin J, Mikolajczak S, Sack B, Fishbaugher M, Seilie A, Shelton L, et al. Complete attenuation of genetically engineered Plasmodium falciparum sporozoites in human subjects. Sci Transl Med. 2017;9: pubmed publisher
    ..parasite by deleting three genes expressed in the pre-erythrocytic stage (Pf p52-/p36-/sap1-)...
  6. Farooq M, Detterbeck A, Clemens S, Dietz K. Silicon-induced reversibility of cadmium toxicity in rice. J Exp Bot. 2016;67:3573-85 pubmed publisher
    ..Reprogramming of the Cd response was obvious for Phytochelatin synthase 1, SAP1 , SAP14, and the transcription factor genes AP2/Erf020, Hsf31, and NAC6 whose transcript levels were strongly ..
  7. He X, Syed K, Tillo D, Mann I, Weirauch M, Vinson C. GABPα Binding to Overlapping ETS and CRE DNA Motifs Is Enhanced by CREB1: Custom DNA Microarrays. G3 (Bethesda). 2015;5:1909-18 pubmed publisher
    ..We show that the ETS-CRE array data can be used to identify regions likely cooperatively bound by GABPα and CREB1 in vivo, and demonstrate their ability to identify human genetic variants that might inhibit cooperative binding. ..
  8. Guan L, He P, Yang F, Zhang Y, Hu Y, Ding J, et al. Sap1 is a replication-initiation factor essential for the assembly of pre-replicative complex in the fission yeast Schizosaccharomyces pombe. J Biol Chem. 2017;292:6056-6075 pubmed publisher
    ..In this study, we identified that the non-ORC protein is Sap1. Like ORC, Sap1 binds to DNA origins during cell growth cycles...
  9. Mizuguchi T, Taneja N, Matsuda E, Belton J, Fitzgerald P, Dekker J, et al. Shelterin components mediate genome reorganization in response to replication stress. Proc Natl Acad Sci U S A. 2017;114:5479-5484 pubmed publisher
    ..Here, we show that fission yeast cells carrying a mutation in the DNA-binding protein Sap1 show defects in DNA replication progression and genome stability and display extensive changes in genome ..
  10. Pericolini E, Gabrielli E, Amacker M, Kasper L, Roselletti E, Luciano E, et al. Secretory Aspartyl Proteinases Cause Vaginitis and Can Mediate Vaginitis Caused by Candida albicans in Mice. MBio. 2015;6:e00724 pubmed publisher
    ..albicans intravaginal injection, and a mutant strain lacking SAP1, SAP2, and SAP3 was unable to cause vaginal inflammation...
  11. Eleftheriadou O, Boguslavskyi A, Longman M, Cowan J, Francois A, Heads R, et al. Expression and regulation of type 2A protein phosphatases and alpha4 signalling in cardiac health and hypertrophy. Basic Res Cardiol. 2017;112:37 pubmed publisher
    ..Although PP6C expression was unchanged, expression of PP6C regulatory subunits (1) Sit4-associated protein 1 (SAP1) and (2) ankyrin repeat domain (ANKRD) 28 and 44 proteins was elevated, whereas SAP2 expression was reduced in ..
  12. Alonso G, Pavarina A, Sousa T, Klein M. A quest to find good primers for gene expression analysis of Candida albicans from clinical samples. J Microbiol Methods. 2018;147:1-13 pubmed publisher
    ..albicans virulence genes: ALS1, CAP1, CAT1, EFG1, HWP1, LIP3, PLB1, SAP1, SAP4, SOD1, SOD5 and ACT1 (normalizing gene)...
  13. Modrzewska B, Kurnatowski P, Khalid K. Comparison of proteolytic activity of Candida sp. strains depending on their origin. J Mycol Med. 2016;26:138-47 pubmed publisher
    ..In total, 61.9% of the strains exhibited the presence of at least one of the SAP1-3 genes in all examined groups, SAP1 being the most common; SAP4-6 genes were not observed...
  14. Tamada M, Zallen J. Square Cell Packing in the Drosophila Embryo through Spatiotemporally Regulated EGF Receptor Signaling. Dev Cell. 2015;35:151-61 pubmed publisher
  15. El Zawawy N, Hafez E. Efficacy of Pluchea dioscoridis leaf extract against pathogenic Candida albicans. J Infect Dev Ctries. 2017;11:334-342 pubmed publisher
    ..albicans. Quantitative changes in phospholipase, hemolysin, and secreted aspartyl proteinase (SAP1 and SAP10) genes expression as virulence factors were analyzed using real-time polymerase chain reaction (RT-PCR)...
  16. Bassyouni R, Wegdan A, Abdelmoneim A, Said W, AboElnaga F. Phospholipase and Aspartyl Proteinase Activities of Candida Species Causing Vulvovaginal Candidiasis in Patients with Type 2 Diabetes Mellitus. J Microbiol Biotechnol. 2015;25:1734-41 pubmed publisher
    ..Detection of aspartyl proteinase genes (SAP1 to SAP8) and phospholipase genes (PLB1, PLB2) were performed by multiplex polymerase chain reaction...
  17. Ramialison M, Waardenberg A, Schonrock N, Doan T, de Jong D, Bouveret R, et al. Analysis of steric effects in DamID profiling of transcription factor target genes. Genomics. 2017;109:75-82 pubmed publisher
    ..the cardiac-restricted transcription factors (TFs) NKX2-5 and SRF, and ubiquitously-expressed co-factors ELK1 and ELK4. We compared targets bound by these TFs as N- and C-terminal fusions with Dam, for both wild type (WT) NKX2-5 and ..
  18. Mori S, Kamei N, Murata Y, Takayama K, Matozaki T, Takeda Morishita M. Microvillus-Specific Protein Tyrosine Phosphatase SAP-1 Plays a Role in Regulating the Intestinal Paracellular Transport of Macromolecules. J Pharm Sci. 2017;106:2904-2908 pubmed publisher
    ..levels of glucose and total cholesterol in the blood were similar between wild-type and SAP-1-deficient mice (Sap1-/-), suggesting no contribution of SAP-1 to biogenic influx...
  19. Qin F, Zhang Y, Liu J, Li H. SLC45A3-ELK4 functions as a long non-coding chimeric RNA. Cancer Lett. 2017;404:53-61 pubmed publisher
    ..This fusion RNA, SLC45A3-ELK4, generated by cis-splicing between neighboring genes, was found in prostate cancer...
  20. Jacobs J, Rosado Lugo J, Cranz Mileva S, Ciccaglione K, Tournier V, Zaratiegui M. Arrested replication forks guide retrotransposon integration. Science. 2015;349:1549-53 pubmed publisher
    ..Here, we show that insertion of the fission yeast LTR retrotransposon Tf1 is guided by the DNA binding protein Sap1 and that the efficiency and location of the targeting depend on the activity of Sap1 as a replication fork barrier...
  21. Bocheńska O, Rapala Kozik M, Wolak N, Aoki W, Ueda M, Kozik A. The action of ten secreted aspartic proteases of pathogenic yeast Candida albicans on major human salivary antimicrobial peptide, histatin 5. Acta Biochim Pol. 2016;63:403-10 pubmed publisher
    ..It was shown that His5 was degraded by seven out of ten Saps (Sap1-4, Sap7-9) over a broad range of pH...
  22. Hickey A, Esnault C, Majumdar A, Chatterjee A, Iben J, McQueen P, et al. Single-Nucleotide-Specific Targeting of the Tf1 Retrotransposon Promoted by the DNA-Binding Protein Sap1 of Schizosaccharomyces pombe. Genetics. 2015;201:905-24 pubmed publisher
    ..We report here that Sap1, an essential DNA-binding protein, plays an important role in Tf1 integration...
  23. Dalton S, Treisman R. Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element. Cell. 1992;68:597-612 pubmed
    ..Ternary complex formation by SAP-1 requires both the ets domain and a second conserved region 50 amino acids to its C-terminal side. SAP-1 has similar DNA binding properties to the previously characterized HeLa cell protein p62/TCF. ..
  24. Zhu C, Johansen F, Prywes R. Interaction of ATF6 and serum response factor. Mol Cell Biol. 1997;17:4957-66 pubmed
    ..ATF6 was previously partially cloned as a member of the ATF family. The complete cDNA of ATF6 was isolated, and its expression pattern was described. ..
  25. Wasylyk B, Hagman J, Gutierrez Hartmann A. Ets transcription factors: nuclear effectors of the Ras-MAP-kinase signaling pathway. Trends Biochem Sci. 1998;23:213-6 pubmed
    ..To direct signals to specific target genes, Ets proteins interact with (other) transcription factors that promote the binding of Ets proteins to composite Ras-responsive elements. ..
  26. Chai Y, Chipitsyna G, Cui J, Liao B, Liu S, Aysola K, et al. c-Fos oncogene regulator Elk-1 interacts with BRCA1 splice variants BRCA1a/1b and enhances BRCA1a/1b-mediated growth suppression in breast cancer cells. Oncogene. 2001;20:1357-67 pubmed
    ..We also observed binding of BRCA1 proteins to other ETS-domain transcription factors SAP1, ETS-1, ERG-2 and Fli-1 but not to Elk-1 splice variant DeltaElk-1 and c-Fos protooncogene...
  27. Janknecht R, Hunter T. Convergence of MAP kinase pathways on the ternary complex factor Sap-1a. EMBO J. 1997;16:1620-7 pubmed
    ..However, signaling from p38 MAP kinase to Sap-1a or from Sap-1a to the basal transcription machinery does not occur in all cell types nor at promoters other than the c-fos SRE, which may ensure the specificity of signaling. ..
  28. Janknecht R, Hunter T. Activation of the Sap-1a transcription factor by the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase. J Biol Chem. 1997;272:4219-24 pubmed
    ..Altogether, our data suggest that Sap-1a plays an important role in the nuclear response elicited by cellular stress. ..
  29. Shipley J, Sheer D, Dalton S, Treisman R, Patel K. Mapping of the human SAP1 (SRF accessory protein 1) gene and SAP2, a gene encoding a related protein, to chromosomal bands 1q32 and 12q23, respectively. Genomics. 1994;23:710-1 pubmed
    b>SAP1, SAP2, and ELK1 form a related subgroup of ETS-domain proteins that can form ternary complexes with the transcription factor SRF at the c-fos serum response element (SRE)...
  30. Stein B, Yang M, Young D, Janknecht R, Hunter T, Murray B, et al. p38-2, a novel mitogen-activated protein kinase with distinct properties. J Biol Chem. 1997;272:19509-17 pubmed
    ..A sequential kinetic mechanism of p38-2 is suggested by steady state kinetic analysis. In conclusion, p38-2 may be an important component of the stress response required for the homeostasis of a cell. ..
  31. Price M, Rogers A, Treisman R. Comparative analysis of the ternary complex factors Elk-1, SAP-1a and SAP-2 (ERP/NET). EMBO J. 1995;14:2589-601 pubmed
    ..Each TCF activation domain can be phosphorylated in vitro by partially purified ERK2, and ERK activation in vivo is sufficient to potentiate transcriptional activation. ..
  32. Sharrocks A, Brown A, Ling Y, Yates P. The ETS-domain transcription factor family. Int J Biochem Cell Biol. 1997;29:1371-87 pubmed
    ..Deregulation of ETS-domain protein activity often leads to tumorigenesis. Future work will uncover further details of how these transcription factors work at the molecular level to regulate specific biological processes. ..
  33. Mo Y, Vaessen B, Johnston K, Marmorstein R. Structures of SAP-1 bound to DNA targets from the E74 and c-fos promoters: insights into DNA sequence discrimination by Ets proteins. Mol Cell. 1998;2:201-12 pubmed
    ..Modeling studies of a SAP-1/SRF/DNA complex suggest that SRF may modulate SAP-1 binding to DNA by interacting with its ETS domain. ..
  34. Yates P, Atherton G, Deed R, Norton J, Sharrocks A. Id helix-loop-helix proteins inhibit nucleoprotein complex formation by the TCF ETS-domain transcription factors. EMBO J. 1999;18:968-76 pubmed
    ..Therefore, our results demonstrate a novel facet of Id function in the coordination of mitogenic signalling and cell cycle entry. ..
  35. Kamakura S, Moriguchi T, Nishida E. Activation of the protein kinase ERK5/BMK1 by receptor tyrosine kinases. Identification and characterization of a signaling pathway to the nucleus. J Biol Chem. 1999;274:26563-71 pubmed
    ..These results reveal a novel signaling pathway to the nucleus mediated by ERK5 that functions downstream of receptor tyrosine kinases to induce immediate early genes, in parallel with the classical MAPK cascade. ..
  36. Cooper S, Trinklein N, Nguyen L, Myers R. Serum response factor binding sites differ in three human cell types. Genome Res. 2007;17:136-44 pubmed
    ..b>ELK4 (previously known as SAP-1 [SRF-associated protein-1]) is ubiquitously expressed...
  37. Peng C, Zeng W, Su J, Kuang Y, He Y, Zhao S, et al. Cyclin-dependent kinase 2 (CDK2) is a key mediator for EGF-induced cell transformation mediated through the ELK4/c-Fos signaling pathway. Oncogene. 2016;35:1170-9 pubmed publisher
    ..Interestingly, CDK2 directly phosphorylates ELK4 at Thr194 and Ser387 and regulates the ELK4 transcriptional activity, which serves as a mechanism to regulate c-fos ..
  38. Hooker E, Baldwin C, Roodman V, Batra A, Isa N, Takano T, et al. Binding and inhibition of the ternary complex factor Elk-4/Sap1 by the adapter protein Dok-4. Biochem J. 2017;474:1509-1528 pubmed publisher
    ..Thus, Dok-4 can target Elk-4 activity through multiple mechanisms, including binding of the transactivation domain, nuclear exclusion and protein destabilization, without a requirement for inhibition of Erk. ..
  39. Hassler M, Richmond T. The B-box dominates SAP-1-SRF interactions in the structure of the ternary complex. EMBO J. 2001;20:3018-28 pubmed
    ..Comparison with a similar region from the yeast MATalpha2-MCM1-DNA complex suggests a common binding motif through which MADS-box proteins may interact with additional factors such as Fli-1. ..
  40. Mo Y, Ho W, Johnston K, Marmorstein R. Crystal structure of a ternary SAP-1/SRF/c-fos SRE DNA complex. J Mol Biol. 2001;314:495-506 pubmed
  41. Jiang L, Xiong J, Zhan J, Yuan F, Tang M, Zhang C, et al. Ubiquitin-specific peptidase 7 (USP7)-mediated deubiquitination of the histone deacetylase SIRT7 regulates gluconeogenesis. J Biol Chem. 2017;292:13296-13311 pubmed publisher
    ..Moreover, SIRT7 targeted the G6PC promoter through the transcription factor ELK4 but not through forkhead box O1 (FoxO1)...
  42. Mingyar E, Novakova R, Knirschova R, Feckova L, Bekeova C, Kormanec J. Unusual features of the large linear plasmid pSA3239 from Streptomyces aureofaciens CCM 3239. Gene. 2018;642:313-323 pubmed publisher
    ..Together with similar proteins from several other linear plasmids (pFRL2, pSLA2-M, pSV2, pSDA1, and SAP1), they constitute a new family of replication initiation proteins...
  43. Maher C, Kumar Sinha C, Cao X, Kalyana Sundaram S, Han B, Jing X, et al. Transcriptome sequencing to detect gene fusions in cancer. Nature. 2009;458:97-101 pubmed publisher
    ..Taken together, this study establishes a robust pipeline for the discovery of novel gene chimaeras using high-throughput sequencing, opening up an important class of cancer-related mutations for comprehensive characterization. ..
  44. Fernández Alvarez A, Soledad Alvarez M, Cucarella C, Casado M. Characterization of the human insulin-induced gene 2 (INSIG2) promoter: the role of Ets-binding motifs. J Biol Chem. 2010;285:11765-74 pubmed publisher
    ..Overall, these results map the functional elements in the human INSIG2 promoter sequence and suggest an unexpected regulation of INSIG2 gene expression in human liver. ..
  45. Giovane A, Sobieszczuk P, Mignon C, Mattei M, Wasylyk B. Locations of the ets subfamily members net, elk1, and sap1 (ELK3, ELK1, and ELK4) on three homologous regions of the mouse and human genomes. Genomics. 1995;29:769-72 pubmed
    ..mouse and human chromosomes (respectively) are net, 10C-D1 and 12q22-q23 (now called ELK3), sap1, 1E3-G and 1q32 (ELK4), and elk1, XA1-A3 and Xp11.2-p11.1 (ELK1), as well as a second locus 14q32 (ELK2) unique to the human genome...
  46. Dalton S, Treisman R. Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element. Cell. 1994;76:411 pubmed
  47. Zhang Y, Gong M, Yuan H, Park H, Frierson H, Li H. Chimeric transcript generated by cis-splicing of adjacent genes regulates prostate cancer cell proliferation. Cancer Discov. 2012;2:598-607 pubmed publisher
    ..Here, we show that a chimeric SLC45A3-ELK4 RNA is generated in the absence of chromosomal rearrangement...
  48. Barber M, Michishita Kioi E, Xi Y, Tasselli L, Kioi M, Moqtaderi Z, et al. SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation. Nature. 2012;487:114-8 pubmed publisher
    ..defined in part by its interaction with the cancer-associated E26 transformed specific (ETS) transcription factor ELK4, and comprises numerous genes with links to tumour suppression...
  49. Qin F, Song Y, Zhang Y, Facemire L, Frierson H, Li H. Role of CTCF in Regulating SLC45A3-ELK4 Chimeric RNA. PLoS ONE. 2016;11:e0150382 pubmed publisher
    The chimeric RNA, SLC45A3-ELK4, was found to be a product of cis-splicing between the two adjacent genes (cis-SAGe). Despite the biological and clinical significance of SLC45A3-ELK4, its generating mechanism has not been elucidated...