Regular ArticleThe MammalianSingle-Minded(SIM) Gene: Mouse cDNA Structure and Diencephalic Expression Indicate a Candidate Gene for Down Syndrome☆
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A recessive variant in SIM2 in a child with complex craniofacial anomalies and global developmental delay
2022, European Journal of Medical GeneticsCitation Excerpt :Human single-minded 2 homolog gene (SIM2) encodes a 667 amino acid protein that is part of a family of basic helix-loop-helix (bHLH) and the PER-ARNT-SIM (PAS) domains transcription factors that play an essential role in central nervous system midline cell development and gene expression (Nambu et al., 1990, 1991). Human SIM2 was initially identified by exon trapping from a Down syndrome critical region (DSCR) on chromosome 21 and was suggested to be a candidate gene for association with many of the pathophysiological features of Down syndrome, including brain development abnormalities, facial dysmorphology, and intellectual impairment, primarily due to its expression at fetal stages of brain development and within regions outside the brain consistent with sites of Down syndrome clinical hallmarks (Rahmani et al., 1989; Chen et al., 1995; Yamaki et al., 1996; Rachidi et al., 2005). However, to date no patients harboring SIM2 point-mutations had been reported, and thus the evidence for causality had been largely due to its location within the DSCR, in which contiguous gene deletions or duplications overlapping SIM2 (up to 70 genes in some reports) cause craniofacial anomalies and various developmental disorders.
Transcription factor single-minded 2 (SIM2) is ubiquitinated by the RING-IBR-RING-type E3 ubiquitin ligases
2005, Experimental Cell ResearchSpatial and temporal localization during embryonic and fetal human development of the transcription factor SIM2 in brain regions altered in Down syndrome
2005, International Journal of Developmental NeuroscienceCitation Excerpt :Sim protein, acting as a tissue-specific partner, is activated by heterodimerisation with Tango, a general dimerization partner, and then transferred to the nucleus where it can bind specific DNA sequences, called CNS-Midline Element (CME) and regulate the expression of target genes, such as hedgehog (hh), involved in the cell-lineage specific development of the CNS (Mellerick and Nirenberg, 1995; Sonnenfeld et al., 1997; Ohshiro and Saigo, 1997; Ward et al., 1998). Similarly to Drosophila sim, the mammalian Sim genes, Sim1 and Sim2, are characterized by restricted expression patterns, particularly in the developing CNS (Dahmane et al., 1995; Ema et al., 1996a,b; Yamaki et al., 1996; Fan et al., 1996). Sim1 and Sim2 proteins interact with the ubiquitous partners Arnt and Arnt2, Tango orthologs, and migrate in the nucleus (Swanson et al., 1995; Probst et al., 1997) where they can activate or repress target genes (Ema et al., 1996a,b; Moffett et al., 1997; Moffett and Pelletier, 2000; Epstein et al., 2000; Woods and Whitelaw, 2002; Liu et al., 2003).
A novel nuclear localization signal in the human single-minded proteins SIM1 and SIM2
2004, Biochemical and Biophysical Research CommunicationsCitation Excerpt :These results exclude Gln389 from the consensus sequence in various SIM proteins. To date, the SIM gene homologs have been isolated from a variety of species including human, mouse, rat, Xenopus, fugu, and zebrafish [4–8]. In these SIM proteins, we found the well-conserved amino acid sequence consisting of a cluster of basic amino acids with Pro and Tyr at the C-terminal end (RKxxKxK/RxxxxKxKxRxxPY) (Fig. 4).
The evolution of chordate neural segmentation
2002, Developmental Biology
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Sequence data from this article have been deposited with the DDBJ/GenBank/EMBL Data Libraries under Accession Nos. D64135 and D70838.
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