Single-minded family bHLH transcription factor 1 | |||||||||||||
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Identifiers | |||||||||||||
Symbols | SIM1 ; bHLHe14 | ||||||||||||
External IDs | OMIM: 603128 MGI: 98306 HomoloGene: 3715 GeneCards: SIM1 Gene | ||||||||||||
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RNA expression pattern | |||||||||||||
More reference expression data | |||||||||||||
Orthologs | |||||||||||||
Species | Human | Mouse | |||||||||||
Entrez | 6492 | 20464 | |||||||||||
Ensembl | ENSG00000112246 | ENSMUSG00000019913 | |||||||||||
UniProt | P81133 | Q61045 | |||||||||||
RefSeq (mRNA) | NM_005068 | NM_011376 | |||||||||||
RefSeq (protein) | NP_005059 | NP_035506 | |||||||||||
Location (UCSC) | Chr 6: 100.83 – 100.91 Mb |
Chr 10: 50.9 – 50.99 Mb |
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PubMed search | [1] | [2] | |||||||||||
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.[1][2][3]
Function
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. Since 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, and/or mental retardation of Down syndrome.[3]
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 [4] and has been suggested to cause a Prader-Willi-like phenotype in other cases.[5] Additionally, studies in mice have shown that haploinsufficieny of Sim1 causes obesity that is due to hyperphagia and do not respond properly to increased dietary fat.[2][6] Overexpression of SIM1 protects against diet induced obesity and rescues the hyperphagia of agouti yellow mice,[7] who have disrupted melanocortin signaling. The obesity and hyperphagia may be mediated by impaired melanocortin activation of PVN neurons [8] and oxytocin deficiency in these mice.[9] It has been demonstrated that modulating Sim1 levels postnatally also leads to hyperphagia and obesity,[10][11] suggesting a physiological role for Sim1 separate from its role in development.
Interactions
SIM1 has been shown to interact with Aryl hydrocarbon receptor nuclear translocator.[12][13]
References
- ^ Chrast R, Scott HS, Chen H, Kudoh J, Rossier C, Minoshima S, Wang Y, Shimizu N, Antonarakis SE (September 1997). "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". Genome Res 7 (6): 615–24. doi:10.1101/gr.7.6.615. PMC 310662. PMID 9199934.
- ^ a b Michaud JL, Boucher F, Melnyk A, Gauthier F, Goshu E, Levy E, Mitchell GA, Himms-Hagen J, Fan CM (July 2001). "Sim1 haploinsufficiency causes hyperphagia, obesity and reduction of the paraventricular nucleus of the hypothalamus". Hum Mol Genet 10 (14): 1465–73. doi:10.1093/hmg/10.14.1465. PMID 11448938.
- ^ a b "Entrez Gene: SIM1 single-minded homolog 1 (Drosophila)".
- ^ Holder JL Jr, Butte NF, Zinn AR (January 2000). "Profound obesity associated with a balanced translocation that disrupts the SIM1 gene". Hum Mol Genet 9 (1): 101–8. doi:10.1093/hmg/9.1.101. PMID 10587584.
- ^ Faivre L, Cormier-Daire V, Lapierre JM, Colleaux L, Jacquemont S, Geneviéve D, Saunier P, Munnich A, Turleau C, Romana S, Prieur M, De Blois MC, Vekemans M (August 2002). "Deletion of the SIM1 gene (6q16.2) in a patient with a Prader-Willi-like phenotype". J Med Genet 39 (8): 594–6. doi:10.1136/jmg.39.8.594. PMC 1735217. PMID 12161602.
- ^ Holder JL Jr, Zhang L, Kublaoui BM, DiLeone RJ, Oz OK, Bair CH, Lee YH, Zinn AR (July 2004). "Sim1 gene dosage modulates the homeostatic feeding response to increased dietary fat in mice". Am J Physiol Endocrinol Metab 287 (1): E105–13. doi:10.1152/ajpendo.00446.2003. PMID 14982752.
- ^ Kublaoui BM, Holder JL Jr, Tolson KP, Gemelli T, Zinn AR (October 2006). "SIM1 overexpression partially rescues agouti yellow and diet-induced obesity by normalizing food intake". Endocrinology 147 (10): 4542–9. doi:10.1210/en.2006-0453. PMID 16709610.
- ^ Kublaoui BM, Holder JL Jr, Gemelli T, Zinn AR (October 2006). "Sim1 haploinsufficiency impairs melanocortin-mediated anorexia and activation of paraventricular nucleus neurons". Mol Endocrinol 20 (10): 2483–92. doi:10.1210/me.2005-0483. PMID 16728530.
- ^ Kublaoui BM, Gemelli T, Tolson KP, Wang Y, Zinn AR (July 2008). "Oxytocin deficiency mediates hyperphagic obesity of Sim1 haploinsufficient mice". Mol Endocrinol 22 (7): 1723–34. doi:10.1210/me.2008-0067. PMC 2453606. PMID 18451093.
- ^ Tolson KP, Gemelli T, Gautron L, Elmquist JK, Zinn AR, Kublaoui BM (March 2010). "Postnatal Sim1 deficiency causes hyperphagic obesity and reduced Mc4r and oxytocin expression". J Neurosci 30 (10): 3803–12. doi:10.1523/JNEUROSCI.5444-09.2010. PMC 3285557. PMID 20220015.
- ^ Yang C, Gagnon D, Vachon P, Tremblay A, Levy E, Massie B, Michaud JL (June 2006). "Adenoviral-mediated modulation of Sim1 expression in the paraventricular nucleus affects food intake". J Neurosci 26 (26): 7116–20. doi:10.1523/JNEUROSCI.0672-06.2006. PMID 16807340.
- ^ Probst, M R; Fan C M; Tessier-Lavigne M; Hankinson O (February 1997). "Two murine homologs of the Drosophila single-minded protein that interact with the mouse aryl hydrocarbon receptor nuclear translocator protein". J. Biol. Chem. (UNITED STATES) 272 (7): 4451–7. doi:10.1074/jbc.272.7.4451. ISSN 0021-9258. PMID 9020169.
- ^ Woods, Susan L; Whitelaw Murray L (March 2002). "Differential activities of murine single minded 1 (SIM1) and SIM2 on a hypoxic response element. Cross-talk between basic helix-loop-helix/per-Arnt-Sim homology transcription factors". J. Biol. Chem. (United States) 277 (12): 10236–43. doi:10.1074/jbc.M110752200. ISSN 0021-9258. PMID 11782478.
Further reading
- Fan CM, Kuwana E, Bulfone A et al. (1996). "Expression patterns of two murine homologs of Drosophila single-minded suggest possible roles in embryonic patterning and in the pathogenesis of Down syndrome.". Mol. Cell. Neurosci. 7 (1): 1–16. doi:10.1006/mcne.1996.0001. PMID 8812055.
- Probst MR, Fan CM, Tessier-Lavigne M, Hankinson O (1997). "Two murine homologs of the Drosophila single-minded protein that interact with the mouse aryl hydrocarbon receptor nuclear translocator protein.". J. Biol. Chem. 272 (7): 4451–7. doi:10.1074/jbc.272.7.4451. PMID 9020169.
- Holder JL, Butte NF, Zinn AR (2000). "Profound obesity associated with a balanced translocation that disrupts the SIM1 gene.". Hum. Mol. Genet. 9 (1): 101–8. doi:10.1093/hmg/9.1.101. PMID 10587584.
- Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination.". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
- Woods SL, Whitelaw ML (2002). "Differential activities of murine single minded 1 (SIM1) and SIM2 on a hypoxic response element. Cross-talk between basic helix-loop-helix/per-Arnt-Sim homology transcription factors.". J. Biol. Chem. 277 (12): 10236–43. doi:10.1074/jbc.M110752200. PMID 11782478.
- Faivre L, Cormier-Daire V, Lapierre JM et al. (2002). "Deletion of the SIM1 gene (6q16.2) in a patient with a Prader-Willi-like phenotype.". J. Med. Genet. 39 (8): 594–6. doi:10.1136/jmg.39.8.594. PMC 1735217. PMID 12161602.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Mungall AJ, Palmer SA, Sims SK et al. (2003). "The DNA sequence and analysis of human chromosome 6.". Nature 425 (6960): 805–11. doi:10.1038/nature02055. PMID 14574404.
- Yamaki A, Kudoh J, Shimizu N, Shimizu Y (2004). "A novel nuclear localization signal in the human single-minded proteins SIM1 and SIM2.". Biochem. Biophys. Res. Commun. 313 (3): 482–8. doi:10.1016/j.bbrc.2003.11.168. PMID 14697214.
- Meyre D, Lecoeur C, Delplanque J et al. (2004). "A genome-wide scan for childhood obesity-associated traits in French families shows significant linkage on chromosome 6q22.31-q23.2.". Diabetes 53 (3): 803–11. doi:10.2337/diabetes.53.3.803. PMID 14988267.
- Kublaoui BM, Holder JL, Tolson KP et al. (2006). "SIM1 overexpression partially rescues agouti yellow and diet-induced obesity by normalizing food intake.". Endocrinology 147 (10): 4542–9. doi:10.1210/en.2006-0453. PMID 16709610.
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