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Gene Review

ESX1  -  ESX homeobox 1

Homo sapiens

Synonyms: ESX1L, ESX1R, ESXR1, Extraembryonic, spermatogenesis, homeobox 1, Homeobox protein ESX1
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Disease relevance of ESX1


High impact information on ESX1

  • Using the Esx1 gene promoter as a model for a Dlx3-responsive gene, studies demonstrate two near consensus Dlx3 binding sites within the proximal 2.3 kb of the transcription start site [2].
  • We also showed that the N-terminal ESXR1 fragment binds to the TAATGTTATTA sequence present within the first intron of the human K-ras gene and inhibits its expression at both mRNA and protein levels [3].
  • ESXR1 is a human paired-like homeodomain-containing protein expressed primarily in the testis [3].
  • In cells, the 65-kDa full-length ESXR1 protein is proteolytically processed into an N-terminal 45-kDa fragment containing the homeodomain, which localizes exclusively within the nucleus, and a C-terminal 20-kDa fragment consisting of a proline-rich repeat region, which is located in the cytoplasm [3].
  • In this work, we demonstrated that the N-terminal ESXR1 fragment specifically recognizes the TAATNNNATTA P3 consensus sequence for the paired-like homeodomain and functions as a sequence-specific transcriptional repressor [3].

Biological context of ESX1

  • Our results indicate that proteolytic processing of ESXR1 plays a role in concerted regulation of the cell cycle and transcription in human cells [4].
  • Accordingly, elevation of ESXR1 level results in accumulation of cyclin A and cyclin B1 and thereby provokes M-phase arrest [4].
  • ESXR1 has been localized to human Xq22.1-q22.3, the same region of synteny shared by the map position of Esx1 [5].
  • Unlike Esx1, ESXR1 contains 12 repeats of a unique nine amino acid motif, PPMAP(V/L)PPG, located C-terminal to the homeodomain [5].
  • A novel human homeobox gene related to the mouse Esx1 homeobox gene, which we have designated ESXR1, has been identified [5].

Anatomical context of ESX1


Associations of ESX1 with chemical compounds


Regulatory relationships of ESX1

  • Paired-like homeodomain protein ESXR1 possesses a cleavable C-terminal region that inhibits cyclin degradation [4].

Other interactions of ESX1

  • In this work, we screened human cDNAs that can rescue yeast Saccharomyces cerevisiae from lethality caused by ectopic expression of human cyclin E and isolated a cDNA encoding ESXR1, a paired-like homeodomain-containing protein with a unique C-terminal proline-rich repeat region [4].
  • ESX1L, a novel X chromosome-linked human homeobox gene expressed in the placenta and testis [5].
  • Identification of ESXR1 as a transcriptional repressor of K-ras has an important implication for the development of cancer therapy that inhibits oncogenic K-Ras expression [3].

Analytical, diagnostic and therapeutic context of ESX1

  • Our RT-PCR analysis showed that ESX1L mRNA is expressed from 5 weeks of gestation until term, suggesting a role not only in trophoblast differentiation but also in the maintenance of the villi and microvasculature [6].
  • Real-time PCR quantitation showed ESX1L levels in control placentae decreased between pre-term and term [0.7 +/- 0.20 (27-35 weeks, n = 13) versus 0.2 +/- 0.06 (36-41 weeks, n = 12), t-test, P < 0.005] [7].


  1. Biparental expression of ESX1L gene in placentas from normal and intrauterine growth-restricted pregnancies. Grati, F.R., Sirchia, S.M., Gentilin, B., Rossella, F., Ramoscelli, L., Antonazzo, P., Cavallari, U., Bulfamante, G., Cetin, I., Simoni, G., Miozzo, M. Eur. J. Hum. Genet. (2004) [Pubmed]
  2. Smad6 represses Dlx3 transcriptional activity through inhibition of DNA binding. Berghorn, K.A., Clark-Campbell, P.A., Han, L., McGrattan, M., Weiss, R.S., Roberson, M.S. J. Biol. Chem. (2006) [Pubmed]
  3. Paired-like homeoprotein ESXR1 acts as a sequence-specific transcriptional repressor of the human K-ras gene. Yanagihara, M., Ishikawa, S., Naito, M., Nakajima, J., Aburatani, H., Hatakeyama, M. Oncogene (2005) [Pubmed]
  4. Paired-like homeodomain protein ESXR1 possesses a cleavable C-terminal region that inhibits cyclin degradation. Ozawa, H., Ashizawa, S., Naito, M., Yanagihara, M., Ohnishi, N., Maeda, T., Matsuda, Y., Jo, Y., Higashi, H., Kakita, A., Hatakeyama, M. Oncogene (2004) [Pubmed]
  5. ESX1L, a novel X chromosome-linked human homeobox gene expressed in the placenta and testis. Fohn, L.E., Behringer, R.R. Genomics (2001) [Pubmed]
  6. Molecular and morphologic analyses of expression of ESX1L in different stages of human placental development. Figueiredo, A.L., Salles, M.G., Albano, R.M., Porto, L.C. J. Cell. Mol. Med. (2004) [Pubmed]
  7. Homeobox gene ESX1L expression is decreased in human pre-term idiopathic fetal growth restriction. Murthi, P., Doherty, V.L., Said, J.M., Donath, S., Brennecke, S.P., Kalionis, B. Mol. Hum. Reprod. (2006) [Pubmed]
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