SIM2
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Gene ontology | |||
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| Location (UCSC) | Chr 21: 36.7 – 36.75 Mb | n/a | |||||||
| PubMed search | [2] | [3] | |||||||
| View/Edit Human | View/Edit Mouse |
Single-minded homolog 2 is a protein that in humans is encoded by the SIM2 gene.[4][5] It plays a major role in the development of the central nervous system midline as well as the construction of the face and head.[6]
Function
Interactions
SIM2 has been shown to
When the SIM2 gene is transfected into
Disease state
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
SIM2 Short (SIM2s)
There are two known isoforms of SIM2 which play different roles in various tissues. The isoform SIM2 Short (SIM2s) has been shown to be specifically expressed in mammary gland tissue.[12] SIM2s is a splice variant which lacks exon 11 of SIM2.[13] It has been researched that SIM2s acts in mammary gland development and has tumor suppressive characteristics specifically in breast cancer.[12][14][15] In a mouse specimen, when SIM2s was not expressed in mammary epithelial cells there were development defects leading to cancer-like characteristics in the cells.[15] The defects were increased cell proliferation, cellular invasion of local stroma, loss of cellular polarity, and loss of E-cadherin cellular adhesion molecules.[15] These observations suggest that SIM2s is essential for proper mammary gland development.[15] Experiments reintroducing SIM2s in human breast cancer cells allowed for the tumor suppressive characteristics to be observed. Comparing normal human breast cells to human breast cancer cells with immunohistochemical staining showed that SIM2s was expressed more in the normal than the cancerous.[12] Reintroducing SIM2s expression in breast cancer cells showed a decrease in growth, proliferation, and invasiveness.[12] SIM2s represses the actions of the matrix metalloprotease-3 gene (MMP3) which include cell migration, cancer progression, and epithelial to mesenchymal transitions (EMT).[12] SIM2s also represses the SLUG transcription factor which in turn suppresses EMT.[15] EMT suppression allows for E-cadherin to remain and for the cell to not undergo pathological EMT associated with tumor formation.[15] These actions show the tumor suppressive effects of SIM2s in mammary epithelium.
Knockout model
Scientists can purposefully "knockout" or cause the gene to be disrupted. To do this, they perform
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000159263 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 7485157.
- ^ a b "Entrez Gene: SIM2 single-minded homolog 2 (Drosophila)".
- ^ S2CID 22828235.
- PMID 9020169.
- PMID 14701734.
- PMID 11782478.
- PMID 9271372.
- S2CID 46238281.
- ^ PMID 16840439.
- PMID 16484282.
- PMID 20150276.
- ^ PMID 18160708.
Further reading
- Dahmane N, Charron G, Lopes C, Yaspo ML, Maunoury C, Decorte L, Sinet PM, Bloch B, Delabar JM (Sep 1995). "Down syndrome-critical region contains a gene homologous to Drosophila sim expressed during rat and human central nervous system development". Proceedings of the National Academy of Sciences of the United States of America. 92 (20): 9191–5. PMID 7568099.
- Chen H, Chrast R, Rossier C, Gos A, Antonarakis SE, Kudoh J, Yamaki A, Shindoh N, Maeda H, Minoshima S (May 1995). "Single-minded and Down syndrome?". Nature Genetics. 10 (1): 9–10. S2CID 12087372.
- Yamaki A, Noda S, Kudoh J, Shindoh N, Maeda H, Minoshima S, Kawasaki K, Shimizu Y, Shimizu N (Jul 1996). "The mammalian single-minded (SIM) gene: mouse cDNA structure and diencephalic expression indicate a candidate gene for Down syndrome". Genomics. 35 (1): 136–43. PMID 8661114.
- Fan CM, Kuwana E, Bulfone A, Fletcher CF, Copeland NG, Jenkins NA, Crews S, Martinez S, Puelles L, Rubenstein JL, Tessier-Lavigne M (Jan 1996). "Expression patterns of two murine homologs of Drosophila single-minded suggest possible roles in embryonic patterning and in the pathogenesis of Down syndrome". Molecular and Cellular Neurosciences. 7 (1): 1–16. S2CID 11411254.
- Osoegawa K, Okano S, Kato Y, Nishimura Y, Soeda E (Jun 1996). "A 19-kb CpG island associated with single-minded gene 2 in Down syndrome chromosomal region". DNA Research. 3 (3): 175–9. PMID 8905236.
- 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. PMID 9020169.
- Chrast R, Scott HS, Chen H, Kudoh J, Rossier C, Minoshima S, Wang Y, Shimizu N, Antonarakis SE (Jun 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 Research. 7 (6): 615–24. PMID 9199934.
- 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. PMID 9271372.
- Dahmane N, Ghezala GA, Gosset P, Chamoun Z, Dufresne-Zacharia MC, Lopes C, Rabatel N, Gassanova-Maugenre S, Chettouh Z, Abramowski V, Fayet E, Yaspo ML, Korn B, Blouin JL, Lehrach H, Poutska A, Antonarakis SE, Sinet PM, Créau N, Delabar JM (Feb 1998). "Transcriptional map of the 2.5-Mb CBR-ERG region of chromosome 21 involved in Down syndrome". Genomics. 48 (1): 12–23. PMID 9503011.
- Ema M, Ikegami S, Hosoya T, Mimura J, Ohtani H, Nakao K, Inokuchi K, Katsuki M, Fujii-Kuriyama Y (Aug 1999). "Mild impairment of learning and memory in mice overexpressing the mSim2 gene located on chromosome 16: an animal model of Down's syndrome". Human Molecular Genetics. 8 (8): 1409–15. PMID 10400987.
- Yamaki A, Tochigi J, Kudoh J, Minoshima S, Shimizu N, Shimizu Y (May 2001). "Molecular mechanisms of human single-minded 2 (SIM2) gene expression: identification of a promoter site in the SIM2 genomic sequence". Gene. 270 (1–2): 265–75. PMID 11404025.
- 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. PMID 11782478.
- Deyoung MP, Scheurle D, Damania H, Zylberberg C, Narayanan R (2003). "Down's syndrome-associated single minded gene as a novel tumor marker". Anticancer Research. 22 (6A): 3149–57. PMID 12530058.
- DeYoung MP, Tress M, Narayanan R (Apr 2003). "Identification of Down's syndrome critical locus gene SIM2-s as a drug therapy target for solid tumors". Proceedings of the National Academy of Sciences of the United States of America. 100 (8): 4760–5. PMID 12676991.
- DeYoung MP, Tress M, Narayanan R (Oct 2003). "Down's syndrome-associated Single Minded 2 gene as a pancreatic cancer drug therapy target". Cancer Letters. 200 (1): 25–31. PMID 14550949.
- Yamaki A, Kudoh J, Shimizu N, Shimizu Y (Jan 2004). "A novel nuclear localization signal in the human single-minded proteins SIM1 and SIM2". Biochemical and Biophysical Research Communications. 313 (3): 482–8. PMID 14697214.
- 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. PMID 14701734.