SIM1

Single-minded homolog 1 also known as class E basic helix-loop-helix protein 14 (bHLHe14) is a is_associated_with::protein that in humans is encoded by the SIM1 is_associated_with::gene.

Function
SIM1 and is_associated_with::SIM2 genes are homologs of is_associated_with::Drosophila melanogaster single-minded (sim), so named because cells in the midline of the sim mutant embryo fail to properly develop and eventually die, and thus the paired longitudinal axon bundles that span the anterior-posterior axis of the embryo (analogous to the embryo's spinal cord) are collapsed into a "single" rudimentary axon bundle at the midline. Sim is a is_associated_with::basic helix-loop-helix-is_associated_with::PAS domain is_associated_with::transcription factor that regulates gene expression in the midline cells. Since the sim gene plays an important role in Drosophila development and has peak levels of expression during the period of is_associated_with::neurogenesis, it was proposed that the human SIM2 gene, which resides in a critical region of chromosome 21, is a candidate for involvement in certain dysmorphic features (particularly facial and skull characteristics), abnormalities of brain development, and/or mental retardation of is_associated_with::Down syndrome.

is_associated_with::Haploinsufficiency of SIM1 has been shown to cause severe early-onset obesity in a human girl with a de novo balanced translocation between chromosomes 1p22.1 and 6q16.2 and has been suggested to cause a Prader-Willi-like phenotype in other cases. Additionally, studies in mice have shown that haploinsufficieny of Sim1 causes obesity that is due to is_associated_with::hyperphagia and do not respond properly to increased dietary fat. Overexpression of SIM1 protects against diet induced obesity and rescues the hyperphagia of agouti yellow mice, who have disrupted is_associated_with::melanocortin signaling. The obesity and hyperphagia may be mediated by impaired melanocortin activation of PVN neurons and is_associated_with::oxytocin deficiency in these mice. It has been demonstrated that modulating Sim1 levels postnatally also leads to hyperphagia and obesity, suggesting a physiological role for Sim1 separate from its role in development.

Interactions
SIM1 has been shown to interact with is_associated_with::Aryl hydrocarbon receptor nuclear translocator.