SIM2

From Wikipedia, the free encyclopedia
Jump to: navigation, search
SIM2
Identifiers
Aliases SIM2, HMC13F06, HMC29C01, SIM, bHLHe15, single-minded family bHLH transcription factor 2
External IDs MGI: 98307 HomoloGene: 3716 GeneCards: 6493
RNA expression pattern
PBB GE SIM2 206558 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005069
NM_009586

NM_011377

RefSeq (protein)

NP_005060.1
NP_033664.2

NP_035507.2

Location (UCSC) Chr 21: 36.7 – 36.75 Mb Chr 16: 94.09 – 94.13 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Single-minded homolog 2 is a protein that in humans is encoded by the SIM2 gene.[1][2] It plays a major role in the development of the central nervous system midline as well as the construction of the face and head.[3]

Function[edit]

SIM1 and SIM2 genes are Drosophila single-minded (sim) gene homologs. The Drosophila sim gene encodes a transcription factor that is a master regulator of neurogenesis of midline cells in the central nervous system. SIM2 maps within the so-called Down syndrome chromosomal region, specifically on the q arm of chromosome 21, band 22.2.[3] Based on the mapping position, its potential function as transcriptional repressor and similarity to Drosophila sim, it is proposed that SIM2 may contribute to some specific Down syndrome phenotypes[2]

Interactions[edit]

SIM2 has been shown to interact with Aryl hydrocarbon receptor nuclear translocator.[4][5][6][7]

When the SIM2 gene is tranfected into PC12 cells, it effects the normal cycle of cell maturation. SIM2 inhibits the expression of cyclin E, which in turn inhibits the cell's ability to pass through the G1/S checkpoint and suppresses the cell's proliferation ability. it also up-regulates the presence of p27, a growth inhibitor protein. The presence of p27 inhibits the activation of cell cycle regulatory kinases.[8]

Disease state[edit]

There are three states of the gene: +/+, +/-, and -/-. When the gene is expressed as SIM2 -/-, it is considered disrupted and many physical malformations are seen, particularly in the craniofacial area. Individuals with SIM2 -/- have either a full or partial secondary palate cleft and malformations in the tongue and pterygoid processes of the sphenoid bone. These malformations cause aerophagia, or the swallowing of air, and postnatal death. Severe aerophagia leads to accumulation of air in the gastrointestinal tract, causing the belly to be distended.[3] It is thought that the over-expression of the SIM2 gene brings about some of the phenotypic deformities that are characteristic of Down syndrome. The presence of SIM2 mRNA in many parts of the brain known to show deformities in individuals with Down syndrome, as well as in the palate, oral and tongue epithelia, mandibular and hyoid bones.[3]

Knockout model[edit]

Scientists can purposefully "knockout" or cause the gene to be disrupted. To do this, they perform homologous recombination and eliminate the predicted start codon and the following 47 amino acids. Then the EcoRI restriction site is introduced into the chromosome.[3]

References[edit]

  1. ^ Muenke M, Bone LJ, Mitchell HF, Hart I, Walton K, Hall-Johnson K, Ippel EF, Dietz-Band J, Kvaløy K, Fan CM (Nov 1995). "Physical mapping of the holoprosencephaly critical region in 21q22.3, exclusion of SIM2 as a candidate gene for holoprosencephaly, and mapping of SIM2 to a region of chromosome 21 important for Down syndrome". American Journal of Human Genetics 57 (5): 1074–9. PMC 1801356. PMID 7485157. 
  2. ^ a b "Entrez Gene: SIM2 single-minded homolog 2 (Drosophila)". 
  3. ^ a b c d e Shamblott, MJ; Bugg, EM; Lawler, AM; Gearhart, JD (2002). "Craniofacial abnormalities resulting from targeted disruption of the murine Sim2 gene.". Developmental Dynamics 2002 (224): 373–380. doi:10.1002/dvdy.10116. 
  4. ^ Probst MR, Fan CM, Tessier-Lavigne M, Hankinson O (Feb 1997). "Two murine homologs of the Drosophila single-minded protein that interact with the mouse aryl hydrocarbon receptor nuclear translocator protein". The Journal of Biological Chemistry 272 (7): 4451–7. doi:10.1074/jbc.272.7.4451. PMID 9020169. 
  5. ^ Ooe N, Saito K, Mikami N, Nakatuka I, Kaneko H (Jan 2004). "Identification of a novel basic helix-loop-helix-PAS factor, NXF, reveals a Sim2 competitive, positive regulatory role in dendritic-cytoskeleton modulator drebrin gene expression". Molecular and Cellular Biology 24 (2): 608–16. doi:10.1128/MCB.24.2.608-616.2004. PMC 343817. PMID 14701734. 
  6. ^ Woods SL, Whitelaw ML (Mar 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". The Journal of Biological Chemistry 277 (12): 10236–43. doi:10.1074/jbc.M110752200. PMID 11782478. 
  7. ^ Moffett P, Reece M, Pelletier J (Sep 1997). "The murine Sim-2 gene product inhibits transcription by active repression and functional interference". Molecular and Cellular Biology 17 (9): 4933–47. doi:10.1128/mcb.17.9.4933. PMC 232345. PMID 9271372. 
  8. ^ Meng, X; Shi, J; Peng, B; Zou, X; Zhang, C. "Effect of mouse Sim2 gene on the cell cycle of PC12 cell.". Cell Biology International 2006 (30): 349–353. doi:10.1016/j.cellbi.2005.11.012. 

Further reading[edit]