{{about|the gene|the console|MSX2|the drug|MSX-2}} {{cs1 config|name-list-style=vanc}} {{Short description|Protein found in humans}} {{Infobox_gene}} '''Homeobox protein MSX-2''' is a protein that in humans is encoded by the ''MSX2'' gene.<ref name="pmid8668339">{{cite journal | vauthors = Takahashi C, Akiyama N, Matsuzaki T, Takai S, Kitayama H, Noda M | title = Characterization of a human MSX-2 cDNA and its fragment isolated as a transformation suppressor gene against v-Ki-ras oncogene | journal = Oncogene | volume = 12 | issue = 10 | pages = 2137–46 | date = May 1996 | pmid = 8668339 }}</ref><ref name="pmid8786091">{{cite journal | vauthors = Kostrzewa M, Grady DL, Moyzis RK, Flöter L, Müller U | title = Integration of four genes, a pseudogene, thirty-one STSs, and a highly polymorphic STRP into the 7-10 Mb YAC contig of 5q34-q35 | journal = Human Genetics | volume = 97 | issue = 3 | pages = 399–403 | date = March 1996 | pmid = 8786091 | doi = 10.1007/BF02185781 | s2cid = 12647370 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: MSX2 msh homeobox 2| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=4488}}</ref>
== Function ==
This gene encodes a member of the muscle segment homeobox gene family. The encoded protein is a transcriptional repressor whose normal activity may establish a balance between survival and apoptosis of neural crest-derived cells required for proper craniofacial morphogenesis. The encoded protein may also have a role in promoting cell growth under certain conditions and may be an important target for the RAS signaling pathways. Mutations in this gene are associated with parietal foramina 1 and craniosynostosis type 2.<ref name="entrez"/> Msx2 is a homeobox gene localized on human chromosome 5 that encodes a transcription repressor and activator (MSX-2) responsible for craniofacial and limb-bud development. Cells will express msx2 when exposed to signaling molecules BMP-2 and BMP-4 in situ.<ref>{{cite journal |last1=Rifas |first1=L |title=Gestational exposure to ethanol suppresses msx2 expression in developing mouse embryos. |journal=Proc Natl Acad Sci U S A |date=July 1997 |volume=94 |issue=14 |pages=7549–54|bibcode=1997PNAS...94.7549R |doi=10.1073/pnas.94.14.7549 |pmid=9207129 |pmc=23859 |doi-access=free }}</ref> It is well documented that expression of cell-cell adhesion molecules such as E-cadherins will promote structural integrity and an epithelial arrangement of cells, while expression of N-cadherin and vimentin promote mesenchymal arrangement and cell migration.<ref>{{cite journal | vauthors = Fujita T, Hayashida K, Shiba H, Kishimoto A, Matsuda S, Takeda K, Kawaguchi H, Kurihara H | title = The expressions of claudin-1 and E-cadherin in junctional epithelium | journal = Journal of Periodontal Research | volume = 45 | issue = 4 | pages = 579–82 | date = August 2010 | pmid = 20337884 | doi = 10.1111/j.1600-0765.2009.01258.x }}</ref><ref>{{cite journal | vauthors = Zhao Y, Yao J, Wu XP, Zhao L, Zhou YX, Zhang Y, You QD, Guo QL, Lu N | title = Wogonin suppresses human alveolar adenocarcinoma cell A549 migration in inflammatory microenvironment by modulating the IL-6/STAT3 signaling pathway | journal = Molecular Carcinogenesis | volume = 54 | pages = E81-93 | date = June 2015 | issue = Suppl 1 | pmid = 24976450 | doi = 10.1002/mc.22182 | s2cid = 29685898 }}</ref> Msx2 downregulates E-cadherins and upregulates N-cadherin and vimentin which indicates its role in inducing epithelial mesenchymal transition (EMT). Germline knockout mice have been created for this gene (Msx2 ±) in order to examine functional loss.<ref>{{cite journal | vauthors = Yu Z, Yu W, Liu J, Wu D, Wang C, Zhang J, Zhao J | title = Lens-specific deletion of the Msx2 gene increased apoptosis by enhancing the caspase-3/caspase-8 signaling pathway | journal = The Journal of International Medical Research | volume = 46 | issue = 7 | pages = 2843–2855 | date = July 2018 | pmid = 29921154 | pmc = 6124292 | doi = 10.1177/0300060518774687 }}</ref> Clinical studies on craniosynostosis, or the premature fusion of cranial structures, have shown the condition to be genetically linked to mutation in the msx2 homeobox gene.<ref>{{cite journal | vauthors = Melville H, Wang Y, Taub PJ, Jabs EW | title = Genetic basis of potential therapeutic strategies for craniosynostosis | journal = American Journal of Medical Genetics. Part A | volume = 152A | issue = 12 | pages = 3007–15 | date = December 2010 | pmid = 21082653 | doi = 10.1002/ajmg.a.33703 | s2cid = 24424024 | doi-access = free }}</ref>
== Interactions ==
Msh homeobox 2 has been shown to interact with DLX5,<ref name=pmid9111364>{{cite journal | vauthors = Zhang H, Hu G, Wang H, Sciavolino P, Iler N, Shen MM, Abate-Shen C | title = Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism | journal = Molecular and Cellular Biology | volume = 17 | issue = 5 | pages = 2920–32 | date = May 1997 | pmid = 9111364 | pmc = 232144 | doi = 10.1128/mcb.17.5.2920 }}</ref> DLX2<ref name=pmid9111364/> and MSX1.<ref name=pmid9111364/>
== References == {{reflist}}
== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Suzuki M, Tanaka M, Iwase T, Naito Y, Sugimura H, Kino I | title = Over-expression of HOX-8, the human homologue of the mouse Hox-8 homeobox gene, in human tumors | journal = Biochemical and Biophysical Research Communications | volume = 194 | issue = 1 | pages = 187–93 | date = July 1993 | pmid = 7687426 | doi = 10.1006/bbrc.1993.1802 | bibcode = 1993BBRC..194..187S | hdl = 10271/1007 | s2cid = 27890243 | hdl-access = free }} * {{cite journal | vauthors = Semenza GL, Wang GL, Kundu R | title = DNA binding and transcriptional properties of wild-type and mutant forms of the homeodomain protein Msx2 | journal = Biochemical and Biophysical Research Communications | volume = 209 | issue = 1 | pages = 257–62 | date = April 1995 | pmid = 7726844 | doi = 10.1006/bbrc.1995.1497 | bibcode = 1995BBRC..209..257S | doi-access = free }} * {{cite journal | vauthors = Iimura T | title = [Molecular cloning and expression of homeobox-containing genes during hard tissue development] | journal = Kokubyo Gakkai Zasshi. The Journal of the Stomatological Society, Japan | volume = 61 | issue = 4 | pages = 590–604 | date = December 1994 | pmid = 7897272 | doi = 10.5357/koubyou.61.590 | s2cid = 2781509 | doi-access = free }} * {{cite journal | vauthors = Hodgkinson JE, Davidson CL, Beresford J, Sharpe PT | title = Expression of a human homeobox-containing gene is regulated by 1,25(OH)2D3 in bone cells | journal = Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression | volume = 1174 | issue = 1 | pages = 11–6 | date = July 1993 | pmid = 8101453 | doi = 10.1016/0167-4781(93)90086-s }} * {{cite journal | vauthors = Jabs EW, Müller U, Li X, Ma L, Luo W, Haworth IS, Klisak I, Sparkes R, Warman ML, Mulliken JB | title = A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis | journal = Cell | volume = 75 | issue = 3 | pages = 443–50 | date = November 1993 | pmid = 8106171 | doi = 10.1016/0092-8674(93)90379-5 | s2cid = 13650758 }} * {{cite journal | vauthors = Ma L, Golden S, Wu L, Maxson R | title = The molecular basis of Boston-type craniosynostosis: the Pro148→His mutation in the N-terminal arm of the MSX2 homeodomain stabilizes DNA binding without altering nucleotide sequence preferences | journal = Human Molecular Genetics | volume = 5 | issue = 12 | pages = 1915–20 | date = December 1996 | pmid = 8968743 | doi = 10.1093/hmg/5.12.1915 | doi-access = free }} * {{cite journal | vauthors = Quinn LM, Johnson BV, Nicholl J, Sutherland GR, Kalionis B | authorlink4=Grant Robert Sutherland | title = Isolation and identification of homeobox genes from the human placenta including a novel member of the Distal-less family, DLX4 | journal = Gene | volume = 187 | issue = 1 | pages = 55–61 | date = March 1997 | pmid = 9073066 | doi = 10.1016/S0378-1119(96)00706-8 }} * {{cite journal | vauthors = Zhang H, Hu G, Wang H, Sciavolino P, Iler N, Shen MM, Abate-Shen C | title = Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism | journal = Molecular and Cellular Biology | volume = 17 | issue = 5 | pages = 2920–32 | date = May 1997 | pmid = 9111364 | pmc = 232144 | doi = 10.1128/mcb.17.5.2920 }} * {{cite journal | vauthors = Wu L, Wu H, Ma L, Sangiorgi F, Wu N, Bell JR, Lyons GE, Maxson R | title = Miz1, a novel zinc finger transcription factor that interacts with Msx2 and enhances its affinity for DNA | journal = Mechanisms of Development | volume = 65 | issue = 1–2 | pages = 3–17 | date = July 1997 | pmid = 9256341 | doi = 10.1016/S0925-4773(97)00032-4 | s2cid = 11835268 | doi-access = }} * {{cite journal | vauthors = Newberry EP, Latifi T, Battaile JT, Towler DA | title = Structure-function analysis of Msx2-mediated transcriptional suppression | journal = Biochemistry | volume = 36 | issue = 34 | pages = 10451–62 | date = August 1997 | pmid = 9265625 | doi = 10.1021/bi971008x }} * {{cite journal | vauthors = Stelnicki EJ, Kömüves LG, Holmes D, Clavin W, Harrison MR, Adzick NS, Largman C | title = The human homeobox genes MSX-1, MSX-2, and MOX-1 are differentially expressed in the dermis and epidermis in fetal and adult skin | journal = Differentiation; Research in Biological Diversity | volume = 62 | issue = 1 | pages = 33–41 | date = October 1997 | pmid = 9373945 | doi = 10.1046/j.1432-0436.1997.6210033.x | doi-access = free }} * {{cite journal | vauthors = Iimura T, Takeda K, Goseki M, Maruoka Y, Sasaki S, Oida S | title = Characterization of two length cDNA for human MSX-2 from dental pulp-derived cells | journal = DNA Sequence | volume = 8 | issue = 1–2 | pages = 87–92 | year = 1998 | pmid = 9522127 | doi = 10.3109/10425179709020891 }} * {{cite journal | vauthors = Newberry EP, Latifi T, Towler DA | title = The RRM domain of MINT, a novel Msx2 binding protein, recognizes and regulates the rat osteocalcin promoter | journal = Biochemistry | volume = 38 | issue = 33 | pages = 10678–90 | date = August 1999 | pmid = 10451362 | doi = 10.1021/bi990967j }} * {{cite journal | vauthors = Wilkie AO, Tang Z, Elanko N, Walsh S, Twigg SR, Hurst JA, Wall SA, Chrzanowska KH, Maxson RE | title = Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification | journal = Nature Genetics | volume = 24 | issue = 4 | pages = 387–90 | date = April 2000 | pmid = 10742103 | doi = 10.1038/74224 | s2cid = 21030594 }} * {{cite journal | vauthors = Wuyts W, Reardon W, Preis S, Homfray T, Rasore-Quartino A, Christians H, Willems PJ, Van Hul W | title = Identification of mutations in the MSX2 homeobox gene in families affected with foramina parietalia permagna | journal = Human Molecular Genetics | volume = 9 | issue = 8 | pages = 1251–5 | date = May 2000 | pmid = 10767351 | doi = 10.1093/hmg/9.8.1251 | doi-access = free }} * {{cite journal | vauthors = Quinn LM, Latham SE, Kalionis B | title = The homeobox genes MSX2 and MOX2 are candidates for regulating epithelial-mesenchymal cell interactions in the human placenta | journal = Placenta | volume = 21 Suppl A | issue = Suppl A | pages = S50-4 | year = 2000 | pmid = 10831122 | doi = 10.1053/plac.1999.0514 }} * {{cite journal | vauthors = Masuda Y, Sasaki A, Shibuya H, Ueno N, Ikeda K, Watanabe K | title = Dlxin-1, a novel protein that binds Dlx5 and regulates its transcriptional function | journal = The Journal of Biological Chemistry | volume = 276 | issue = 7 | pages = 5331–8 | date = February 2001 | pmid = 11084035 | doi = 10.1074/jbc.M008590200 | doi-access = free }} * {{cite journal | vauthors = Shirakabe K, Terasawa K, Miyama K, Shibuya H, Nishida E | title = Regulation of the activity of the transcription factor Runx2 by two homeobox proteins, Msx2 and Dlx5 | journal = Genes to Cells | volume = 6 | issue = 10 | pages = 851–6 | date = October 2001 | pmid = 11683913 | doi = 10.1046/j.1365-2443.2001.00466.x | s2cid = 22071040 | doi-access = free }} {{refend}}
== External links == * [https://www.ncbi.nlm.nih.gov/books/NBK1128/ GeneReviews/NCBI/UW/NIH entry on Enlarged Parietal Foramina/Cranium Bifidum] * {{MeshName|MSX2+protein,+human}} * {{UCSC genome browser|MSX2}} * {{UCSC gene details|MSX2}}
{{NLM content}} {{PDB Gallery|geneid=4488}} {{Transcription factors|g3}}
{{DEFAULTSORT:Msh Homeobox 2}} Category:Transcription factors Category:Human proteins