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Gene Review

SIM1  -  single-minded family bHLH transcription...

Homo sapiens

Synonyms: BHLHE14, Class E basic helix-loop-helix protein 14, Single-minded homolog 1, bHLHe14
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Disease relevance of SIM1


Psychiatry related information on SIM1

  • The basic helix-loop-helix PAS (bHLH-PAS) transcription factors SIM1 and arylhydrocarbon receptor (AHR) are involved in the control of feeding behavior [7].

High impact information on SIM1

  • Severe obesity was described recently in a patient with a balanced translocation disrupting SIM1 [8].
  • The bHLH-PAS transcription factor SIM1 is required for the development of the paraventricular nucleus (PVN) of the hypothalamus [8].
  • Mouse Sim1 is expressed in the developing kidney and central nervous system, and is essential for formation of the supraoptic and paraventricular (PVN) nuclei of the hypothalamus [3].
  • The bHLH-PAS transcription factors SIM1 and SIM2 are co-expressed in the developing MB [9].
  • LFP cells are induced by the MFP to express HNF3beta transiently, Shh continuously and other floor-plate characteristic genes such as NETRIN: In contrast to MFP cells, LFP cells also express neural markers such as Nkx2.2 and Sim1 [10].

Biological context of SIM1

  • Regulatory interaction between arylhydrocarbon receptor and SIM1, two basic helix-loop-helix PAS proteins involved in the control of food intake [7].
  • SIM1 inhibits binding of the AHR.ARNT dimer to the xenobiotic response element in vitro [4].
  • Thus mouse SIM1 and SIM2 are novel heterodimerization partners for ARNT in vitro, and they may function both as positive and negative transcriptional regulators in vivo, during embryogenesis and in the adult organism [4].
  • Transfection assay showed the presence of NLS activity in the small region of 23 and 21 amino acid residues at the central part of SIM2 and SIM1 proteins, respectively [11].
  • Human Single-minded 1 (SIM1) and SIM2 genes were found as homologs of Drosophila sim gene which plays a key role in the midline cell lineage of the central nervous system [11].

Anatomical context of SIM1

  • In cell lines engineered to stably express SIM1 and SIM2, we show that both are nuclear proteins that constitutively complex with the general bHLH/PAS partner factor, ARNT [1].
  • In adult mice mRNA for SIM1 was expressed in lung, skeletal muscle, and kidney, whereas the mRNA for SIM2 was found in the latter two [4].
  • The bHLH-PAS transcription factor SIM1 is required for the development of neurons of the anterior hypothalamus (AH) [12].
  • An imbalance of 2 mm in the right direction at the 8th thoracic vertebra was imposed and two simulations were performed: one with only growth modulation perpendicular to growth plates (Sim1), and the other one with additional components in the transverse plane (Sim2) [13].

Associations of SIM1 with chemical compounds


Other interactions of SIM1

  • Possible candidate genes in this region include SIM1, MCHR2, and PC-1 [15].
  • The reference sequences of all genes encoding IMP and VIM types, SPM-1, GIM-1, and SIM-1 were downloaded from GenBank, and primers were designed to obtain amplicons showing different sizes and melting peak temperatures (T(m)) [16].

Analytical, diagnostic and therapeutic context of SIM1

  • Northern blot analysis revealed one mRNA SIM1 species of approximately 9.5 kb and four different mRNA SIM2 species of 2.7, 3, 4.4, and 6 kb in human fetal kidney [2].
  • Three proteins with molecular weights of 300,000, 185,000, and 90,000 were isolated from SIM-1 membrane extracts by HBA-71 affinity chromatography [5].
  • All of these genes are expressed in domains that are contained within that of Sim1 and their expression is changed in Sim1(-/-) embryos as predicted by the microarray analysis [12].


  1. Differential activities of murine single minded 1 (SIM1) and SIM2 on a hypoxic response element. Cross-talk between basic helix-loop-helix/per-Arnt-Sim homology transcription factors. Woods, S.L., Whitelaw, M.L. J. Biol. Chem. (2002) [Pubmed]
  2. Cloning of two human homologs of the Drosophila single-minded gene SIM1 on chromosome 6q and SIM2 on 21q within the Down syndrome chromosomal region. Chrast, R., Scott, H.S., Chen, H., Kudoh, J., Rossier, C., Minoshima, S., Wang, Y., Shimizu, N., Antonarakis, S.E. Genome Res. (1997) [Pubmed]
  3. Profound obesity associated with a balanced translocation that disrupts the SIM1 gene. Holder, J.L., Butte, N.F., Zinn, A.R. Hum. Mol. Genet. (2000) [Pubmed]
  4. Two murine homologs of the Drosophila single-minded protein that interact with the mouse aryl hydrocarbon receptor nuclear translocator protein. Probst, M.R., Fan, C.M., Tessier-Lavigne, M., Hankinson, O. J. Biol. Chem. (1997) [Pubmed]
  5. Characterization of a human endocrine tissue and tumor-associated Ewing's sarcoma antigen. Hamilton, G., Fellinger, E.J., Schratter, I., Fritsch, A. Cancer Res. (1988) [Pubmed]
  6. SIM1 overexpression partially rescues agouti yellow and diet-induced obesity by normalizing food intake. Kublaoui, B.M., Holder, J.L., Tolson, K.P., Gemelli, T., Zinn, A.R. Endocrinology (2006) [Pubmed]
  7. Regulatory interaction between arylhydrocarbon receptor and SIM1, two basic helix-loop-helix PAS proteins involved in the control of food intake. Yang, C., Boucher, F., Tremblay, A., Michaud, J.L. J. Biol. Chem. (2004) [Pubmed]
  8. Sim1 haploinsufficiency causes hyperphagia, obesity and reduction of the paraventricular nucleus of the hypothalamus. Michaud, J.L., Boucher, F., Melnyk, A., Gauthier, F., Goshu, E., Lévy, E., Mitchell, G.A., Himms-Hagen, J., Fan, C.M. Hum. Mol. Genet. (2001) [Pubmed]
  9. Sim1 and Sim2 are required for the correct targeting of mammillary body axons. Marion, J.F., Yang, C., Caqueret, A., Boucher, F., Michaud, J.L. Development (2005) [Pubmed]
  10. Dual origin of the floor plate in the avian embryo. Charrier, J.B., Lapointe, F., Le Douarin, N.M., Teillet, M.A. Development (2002) [Pubmed]
  11. A novel nuclear localization signal in the human single-minded proteins SIM1 and SIM2. Yamaki, A., Kudoh, J., Shimizu, N., Shimizu, Y. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  12. Laminar organization of the early developing anterior hypothalamus. Caqueret, A., Boucher, F., Michaud, J.L. Dev. Biol. (2006) [Pubmed]
  13. Simulation of progressive deformities in adolescent idiopathic scoliosis using a biomechanical model integrating vertebral growth modulation. Villemure, I., Aubin, C.E., Dansereau, J., Labelle, H. Journal of biomechanical engineering. (2002) [Pubmed]
  14. Novel acquired metallo-beta-lactamase gene, bla(SIM-1), in a class 1 integron from Acinetobacter baumannii clinical isolates from Korea. Lee, K., Yum, J.H., Yong, D., Lee, H.M., Kim, H.D., Docquier, J.D., Rossolini, G.M., Chong, Y. Antimicrob. Agents Chemother. (2005) [Pubmed]
  15. A genome-wide scan for childhood obesity-associated traits in French families shows significant linkage on chromosome 6q22.31-q23.2. Meyre, D., Lecoeur, C., Delplanque, J., Francke, S., Vatin, V., Durand, E., Weill, J., Dina, C., Froguel, P. Diabetes (2004) [Pubmed]
  16. Rapid Detection and Identification of Metallo-{beta}-Lactamase-Encoding Genes by Multiplex Real-Time PCR Assay and Melt Curve Analysis. Mendes, R.E., Kiyota, K.A., Monteiro, J., Castanheira, M., Andrade, S.S., Gales, A.C., Pignatari, A.C., Tufik, S. J. Clin. Microbiol. (2007) [Pubmed]
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