Disease relevance of SIM1

• SIM protein levels decrease with hypoxia treatment in our stable cell lines, although levels of the transcripts encoding SIM1 and SIM2 and the approximately 2-h half-lives of each protein are unchanged during hypoxia [1].
• 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 [2].
• Profound obesity associated with a balanced translocation that disrupts the SIM1 gene [3].
• Introduction of SIM1 into hepatoma cells inhibits transcriptional transactivation by the endogenous AHR.ARNT dimer [4].
• A new cell line (SIM-1) was derived from a peripheral neuroectodermal tumor (PNET) and used for the production of a monoclonal antibody (HBA-71), which recognizes a novel cell surface antigen of ES- and PNET-derived cells and paraffin-embedded tumor sections [5].
• The SIM1 transgene also completely rescued the hyperphagia and partially rescued the obesity of agouti yellow mice, in which melanocortin signaling is abrogated [6].

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

• All SIM-1-producing isolates exhibited relatively low imipenem and meropenem MICs (8 to 16 microg/ml) and had a multidrug resistance phenotype [14].

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].

References