SIM1

SIM1
Identifiers
Aliases	SIM1, bHLHe14, single-minded family bHLH transcription factor 1, SIM bHLH transcription factor 1
External IDs	OMIM: 603128; MGI: 98306; HomoloGene: 3715; GeneCards: SIM1; OMA:SIM1 - orthologs
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6q16.3 Start 100,385,009 bp[1] End 100,464,921 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 B3|10 24.87 cM Start 50,770,850 bp[2] End 50,865,248 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in renal medulla Skeletal muscle tissue of biceps brachii human penis Skeletal muscle tissue of rectus abdominis corpus epididymis caput epididymis testicle vastus lateralis muscle islet of Langerhans kidney tubule Top expressed in supraoptic nucleus inner renal medulla paraventricular nucleus of hypothalamus lumbar subsegment of spinal cord mammillary body right kidney dorsomedial hypothalamic nucleus soleus muscle outer renal medulla Bowman's capsule More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA-binding transcription factor activity DNA binding protein dimerization activity protein heterodimerization activity DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus Biological process regulation of transcription by RNA polymerase II multicellular organism development cell differentiation ureteric bud development regulation of transcription, DNA-templated transcription, DNA-templated nervous system development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6492 20464 Ensembl ENSG00000112246 ENSMUSG00000019913 UniProt P81133 Q61045 RefSeq (mRNA) NM_005068 NM_001374769 NM_011376 RefSeq (protein) NP_005059 NP_001361698 NP_035506 Location (UCSC) Chr 6: 100.39 – 100.46 Mb Chr 10: 50.77 – 50.87 Mb PubMed search [3] [4]
Wikidata
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Single-minded homolog 1, also known as class E basic helix-loop-helix protein 14 (bHLHe14), is a protein that in humans is encoded by the SIM1 gene.^[5][6][7]

The SIM1 and SIM2 genes are homologs of 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 basic helix-loop-helix–PAS domain transcription factor that regulates gene expression in the midline cells. Because the sim gene plays an important role in Drosophila development and has peak levels of expression during the period of 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, or mental retardation of Down syndrome.^[7]

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^[8] and has been suggested to cause a Prader-Willi-like phenotype in other cases.^[9] Additionally, studies in mice have shown that haploinsufficiency of Sim1 causes obesity that is due to hyperphagia and do not respond properly to increased dietary fat.^[6][10] Overexpression of SIM1 protects against diet induced obesity and rescues the hyperphagia of agouti yellow mice,^[11] who have disrupted melanocortin signaling. The obesity and hyperphagia may be mediated by impaired melanocortin activation of PVN neurons^[12] and oxytocin deficiency in these mice.^[13] It has been demonstrated that modulating SIM1 levels postnatally also leads to hyperphagia and obesity,^[14][15] suggesting a physiological role for SIM1 separate from its role in development.

SIM1 has been shown to interact with aryl hydrocarbon receptor nuclear translocator.^[16][17]