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FLASH GENE
Symbol SIM1 contributors: mct - updated : 10-10-2018
HGNC name single-minded homolog 1 (Drosophila)
HGNC id 10882
DNA
TYPE functioning gene
STRUCTURE 74.80 kb     11 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Binding site   enhancer
text structure
  • two brain enhancers in the SIM1 locus with a set of obesity-specific SNPs within one of them, which may predispose individuals to obesity
    • MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 3995 85.4 766 - PMID: 9199934
    EXPRESSION
    Type
    constitutive of
       expressed in (based on citations)
    organ(s)
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text in developing kidney, pancreas
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • basic helix-loop-helix (bHLH)
  • a stretch of approximately 300AA, termed the PAS (period - ARNT - Sim) region
  • NLS consisting of a cluster of basic amino acids with Pro and Tyr at the C-terminal
    • HOMOLOGY
    interspecies homolog to Drosophila (single minded 1) Sim1
    ortholog to murine Sim1
    Homologene
    FAMILY
  • BHLH/PAS transcription factor family
    • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • master regulator of fruit fly midline neurogenesis
  • required for the development of all neurons of the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus
  • playing an essential role for formation of the supraoptic and paraventricular(PVN) nuclei of the hypothalamus, PVN implicated in the regulation of body weight
  • role in feeding regulation not limited to formation of the paraventricular nuclei
  • ARNT2 and SIM1 are required to determine the lateral position of neuroendocrine and dopaminergic (DA) longitudinal axons en route to the spinal cord
  • ARNT2 and SIM1 transcription factors contribute to proper positioning of Hypothalamic projections into the spinal cord (HTS)longitudinal axon tracts
  • is a transcription factor involved in brain patterning and control of energy balance
  • transcription factor SIM1 (single-minded 1) is important for development and function of regions of the hypothalamus that regulate energy homoeostasis and the feeding response
  • is a basic helix-loop-helix Per-Arnt-Sim transcription factor that is important for neuronal development in the hypothalamus
  • SIM1 is a critical yet previously unrecognized modulator of skeletal homeostasis that functions through a central relay
  • has an established role in body weight homeostasis and sexual function
    • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimerizing with ARNT2 and acting in neuroendocrine hypothalamus development
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • cofactor of ARNT2 (are required for expression of POU3F2 during hypothalamic development)
  • MAGED1 binds and positively regulates the transcriptional activity of family members SIM1, SIM2, NPAS4 and ARNT2, but does not interact with AHR, HIF1A and ARNT
  • melanocortin signaling via the MC4R on SIM1 neurons implicated in the central control of male sexual behavior
    • cell & other
    REGULATION
    Other regulated by neural protein OLIG2 (OLIG2 acts upstream of the transcriptional regulator SIM1 to specify diencephalic dopaminergic neuron)
    ASSOCIATED DISORDERS
    corresponding disease(s) DEL6QP
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    postnatal CNS deficiency of SIM1 is sufficient to cause hyperphagic obesity (Tolson 2010)
    constitutional       loss of function
    causes early-onset obesity
    constitutional germinal mutation     loss of function
    in overweight children with developmental delay
    Susceptibility
  • to erectile dysfunction
  • to obesity associated with lower preference for high sugar and low fat
    • Variant & Polymorphism SNP
  • rs17185536-T significantly associated with the risk of erectile dysfunction
  • SIM1 variant, p.D134N, associated to obesity associated with lower preference for high sugar and low fat
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • murine S-/- die perinatally, Sim+/- development early-onset obesity, with hyperphagy but not decrease of energy expenditure
  • Sim1-overexpressing transgenic mice exhibit decreased bone formation and low bone mass
  • paraventricular nucleus (PVN)-Sim1 neuron ablated mice have a decreased response to fasting-induced hyperphagia