Homeoboks 2

Homeoboksni protein MSX-2 je protein koji je kod ljudi kodiran genom MSX2 sa hromosoma 5, sekvenca 5q34-q35.^[5][6][7]

Homeoboks 2
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 3RKQ, 4S0H
Identifikatori
Aliasi	NKX2-5
Vanjski ID-jevi	OMIM: 600584 MGI: 97350 HomoloGene: 3230 GeneCards: NKX2-5
Lokacija gena (čovjek) Hrom. Hromosom 5 (čovjek)[1] Bend 5q35.1 Početak 173,232,109 bp[1] Kraj 173,235,311 bp[1]
Lokacija gena (miš) Hrom. Hromosom 17 (miš)[2] Bend 17 A3.3|17 13.6 cM Početak 27,057,638 bp[2] Kraj 27,063,983 bp[2]
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • transcription factor binding • protein homodimerization activity • serum response element binding • chromatin binding • GO:0001948, GO:0016582 vezivanje za proteine • vezivanje sa DNK • sequence-specific DNA binding • GO:0001104 transcription coregulator activity • protein heterodimerization activity • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific Ćelijska komponenta • citoplazma • jedro • transcription regulator complex • RNA polymerase II transcription regulator complex • GO:0009327 makromolekulani kompleks • protein-DNA complex Biološki proces • cardiac conduction system development • apoptotic process involved in heart morphogenesis • bundle of His development • GO:0044324, GO:0003256, GO:1901213, GO:0046019, GO:0046020, GO:1900094, GO:0061216, GO:0060994, GO:1902064, GO:0003258, GO:0072212 regulation of transcription by RNA polymerase II • atrioventricular node cell development • outflow tract morphogenesis • embryonic heart tube development • Vaskulogeneza • heart looping • atrial septum morphogenesis • positive regulation of heart contraction • proepicardium development • pulmonary myocardium development • heart contraction • ventricular cardiac muscle cell development • negative regulation of canonical Wnt signaling pathway • pharyngeal system development • atrioventricular node development • cardiac ventricle formation • GO:0009373 regulation of transcription, DNA-templated • cardiac muscle contraction • regulation of cardiac muscle cell proliferation • heart trabecula formation • ventricular septum morphogenesis • cardiac muscle cell differentiation • Purkinje myocyte differentiation • spleen development • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated • heart development • positive regulation of neuron differentiation • positive regulation of cardioblast differentiation • septum secundum development • atrial cardiac muscle cell development • Ćelijska diferencijacija • adult heart development • right ventricular cardiac muscle tissue morphogenesis • negative regulation of apoptotic process • GO:1901227 negative regulation of transcription by RNA polymerase II • positive regulation of transcription initiation from RNA polymerase II promoter • cardiac muscle cell proliferation • BMP signaling pathway • ventricular trabecula myocardium morphogenesis • outflow tract septum morphogenesis • negative regulation of cardiac muscle cell apoptotic process • thyroid gland development • canonical Wnt signaling pathway • GO:0045996 negative regulation of transcription, DNA-templated • sarcomere organization • cardiac ventricle morphogenesis • regulation of cardiac conduction • cardiac muscle tissue development • embryonic heart tube left/right pattern formation • heart morphogenesis • cardiac muscle tissue morphogenesis • multicellular organism development • GO:1901313 positive regulation of gene expression • positive regulation of cell population proliferation • GO:0061423 positive regulation of sodium ion transport • negative regulation of myotube differentiation • regulation of cardiac muscle contraction • ventricular cardiac myofibril assembly • atrioventricular node cell fate commitment • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II • transcription by RNA polymerase II • Hematopoeza Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	1482	18091
Ensembl	ENSG00000183072	ENSMUSG00000015579
UniProt	P52952	P42582
RefSeq (mRNK)	NM_004387 NM_001166175 NM_001166176	NM_008700
RefSeq (bjelančevina)	NP_001159647 NP_001159648 NP_004378	NP_032726
Lokacija (UCSC)	Chr 5: 173.23 – 173.24 Mb	Chr 17: 27.06 – 27.06 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 267 aminokiselina, a molekulska težina 28 897 Da.^[8]

• C: Cistein
• D: Asparaginska kiselina
• E: Glutaminska kiselina
• F: Fenilalanin
• G: Glicin
• H: Histidin
• I: Izoleucin
• K: Lizin
• L: Leucin
• M: Metionin
• N: Asparagin
• P: Prolin
• Q: Glutamin
• R: Arginin
• S: Serin
• T: Treonin
• V: Valin
• W: Triptofan
• Y: Tirozin

10		20		30		40		50
MASPSKGNDL		FSPDEEGPAV		VAGPGPGPGG		AEGAAEERRV		KVSSLPFSVE
ALMSDKKPPK		EASPLPAESA		SAGATLRPLL		LSGHGAREAH		SPGPLVKPFE
TASVKSENSE		DGAAWMQEPG		RYSPPPRHMS		PTTCTLRKHK		TNRKPRTPFT
TSQLLALERK		FRQKQYLSIA		ERAEFSSSLN		LTETQVKIWF		QNRRAKAKRL
QEAELEKLKM		AAKPMLPSSF		SLPFPISSPL		QAASIYGASY		PFHRPVLPIP
PVGLYATPVG		YGMYHLS

Funkcija

Ovaj gen kodira člana porodice homeoboksnih gena mišićnog segmenta. Kodirani protein je transkripcijski represor čija normalna aktivnost može uspostaviti ravnotežu između preživljavanja i apoptoze ćelija izvedenih iz nevnog grebena, potrebnih za pravilnu kraniofacijsku morfogenezu. Kodirani protein takođe može imati ulogu u promociji rasta ćelija pod određenim uslovima i može biti važna meta za RAS signalne puteve. Mutacije ovog gena su povezane sa tjemenim otvorom 1 i kraniosinostozom tip 2.^[7]

Msx2 je homeoboksni gen lokaliziran na ljudskom hromosomu 5, ai kodira represor i aktivator transkripcije (MSX-2) odgovoran za kraniofacijalni razvoj i razvoj pupoljaka udova. Ćelije eksprimiraju msx2 kada su izložene signalnim molekulama BMP-2 i BMP-4 in situ.^[9] Ekspresija msx2 dovodi do proliferacije, migracije i osteogene diferencijacije ćelija nervnog grebena tokom embriogeneze i frakture kosti.^[10] Dobro je dokumentovano da će ekspresija adhezjskih molekula ćelija-ćelija, kao što su E-kadherini, promovirati strukturni integritet i epitelni raspored ćelija, dok ekspresija N-kadherina i vimentina promoviše mezenhimski raspored i migraciju ćelija.^[11][12] Msx2 smanjuje regulaciju E-kadherina i povećava N-kadherin i vimentin, što ukazuje na njegovu ulogu u izazivanju epitelne mezenhimske tranzicije (EMT). Za ovaj gen kreirani miševi genotipa (Msx2 +/–) nokautiranjem zametne linije kako bi se ispitao funkcionalni gubitak.^[13] Kliničke studije o kraniosinostozi, ili preranoj fuziji kranijalnih struktura, pokazale su da je ovo stanje genetički povezano s mutacijom homeoboksnog gena msx2.^[14]

Interakcije

Pokazalo se da Msh homeoboks 2 reaguje sa DLX5,^[15] DLX2^[15] i MSX1.^[15]

Reference

1. GRCh38: Ensembl release 89: ENSG00000183072 - Ensembl, maj 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000015579 - Ensembl, maj 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Takahashi C, Akiyama N, Matsuzaki T, Takai S, Kitayama H, Noda M (maj 1996). "Characterization of a human MSX-2 cDNA and its fragment isolated as a transformation suppressor gene against v-Ki-ras oncogene". Oncogene. 12 (10): 2137–46. PMID 8668339.
6. Kostrzewa M, Grady DL, Moyzis RK, Flöter L, Müller U (mart 1996). "Integration of four genes, a pseudogene, thirty-one STSs, and a highly polymorphic STRP into the 7-10 Mb YAC contig of 5q34-q35". Human Genetics. 97 (3): 399–403. doi:10.1007/BF02185781. PMID 8786091. S2CID 12647370.
7. "Entrez Gene: MSX2 msh homeobox 2".
8. "UniProt, P35548" (jezik: engleski). Pristupljeno 27. 12. 2021.
9. Rifas, L (juli 1997). "Gestational exposure to ethanol suppresses msx2 expression in developing mouse embryos". Proc Natl Acad Sci U S A. 94 (14): 7549–54. Bibcode:1997PNAS...94.7549R. doi:10.1073/pnas.94.14.7549. PMC 23859. PMID 9207129.
10. Liu H, Chen B, Li Y (mart 2019). "microRNA-203 promotes proliferation, differentiation, and migration of osteoblasts by upregulation of Msh homeobox 2". Journal of Cellular Physiology. 234 (10): 17639–17648. doi:10.1002/jcp.28387. PMID 30854680. S2CID 73726197.
11. Fujita T, Hayashida K, Shiba H, Kishimoto A, Matsuda S, Takeda K, Kawaguchi H, Kurihara H (august 2010). "The expressions of claudin-1 and E-cadherin in junctional epithelium". Journal of Periodontal Research. 45 (4): 579–82. doi:10.1111/j.1600-0765.2009.01258.x. PMID 20337884.
12. Zhao Y, Yao J, Wu XP, Zhao L, Zhou YX, Zhang Y, You QD, Guo QL, Lu N (juni 2015). "Wogonin suppresses human alveolar adenocarcinoma cell A549 migration in inflammatory microenvironment by modulating the IL-6/STAT3 signaling pathway". Molecular Carcinogenesis. 54 Suppl 1: E81-93. doi:10.1002/mc.22182. PMID 24976450. S2CID 29685898.
13. Yu Z, Yu W, Liu J, Wu D, Wang C, Zhang J, Zhao J (juli 2018). "Lens-specific deletion of the Msx2 gene increased apoptosis by enhancing the caspase-3/caspase-8 signaling pathway". The Journal of International Medical Research. 46 (7): 2843–2855. doi:10.1177/0300060518774687. PMC 6124292. PMID 29921154.
14. Melville H, Wang Y, Taub PJ, Jabs EW (decembar 2010). "Genetic basis of potential therapeutic strategies for craniosynostosis". American Journal of Medical Genetics. Part A. 152A (12): 3007–15. doi:10.1002/ajmg.a.33703. PMID 21082653. S2CID 24424024.
15. Zhang H, Hu G, Wang H, Sciavolino P, Iler N, Shen MM, Abate-Shen C (maj 1997). "Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism". Molecular and Cellular Biology. 17 (5): 2920–32. doi:10.1128/mcb.17.5.2920. PMC 232144. PMID 9111364.

Dopunska literatura

• Suzuki M, Tanaka M, Iwase T, Naito Y, Sugimura H, Kino I (juli 1993). "Over-expression of HOX-8, the human homologue of the mouse Hox-8 homeobox gene, in human tumors". Biochemical and Biophysical Research Communications. 194 (1): 187–93. doi:10.1006/bbrc.1993.1802. hdl:10271/1007. PMID 7687426.
• Semenza GL, Wang GL, Kundu R (april 1995). "DNA binding and transcriptional properties of wild-type and mutant forms of the homeodomain protein Msx2". Biochemical and Biophysical Research Communications. 209 (1): 257–62. doi:10.1006/bbrc.1995.1497. PMID 7726844.
• Iimura T (decembar 1994). "[Molecular cloning and expression of homeobox-containing genes during hard tissue development]". Kokubyo Gakkai Zasshi. The Journal of the Stomatological Society, Japan. 61 (4): 590–604. doi:10.5357/koubyou.61.590. PMID 7897272. S2CID 2781509.
• Hodgkinson JE, Davidson CL, Beresford J, Sharpe PT (juli 1993). "Expression of a human homeobox-containing gene is regulated by 1,25(OH)2D3 in bone cells". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1174 (1): 11–6. doi:10.1016/0167-4781(93)90086-s. PMID 8101453.
• Jabs EW, Müller U, Li X, Ma L, Luo W, Haworth IS, Klisak I, Sparkes R, Warman ML, Mulliken JB (novembar 1993). "A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis". Cell. 75 (3): 443–50. doi:10.1016/0092-8674(93)90379-5. PMID 8106171. S2CID 13650758.
• Ma L, Golden S, Wu L, Maxson R (decembar 1996). "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". Human Molecular Genetics. 5 (12): 1915–20. doi:10.1093/hmg/5.12.1915. PMID 8968743.
• Quinn LM, Johnson BV, Nicholl J, Sutherland GR, Kalionis B (mart 1997). "Isolation and identification of homeobox genes from the human placenta including a novel member of the Distal-less family, DLX4". Gene. 187 (1): 55–61. doi:10.1016/S0378-1119(96)00706-8. PMID 9073066.
• Zhang H, Hu G, Wang H, Sciavolino P, Iler N, Shen MM, Abate-Shen C (maj 1997). "Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism". Molecular and Cellular Biology. 17 (5): 2920–32. doi:10.1128/mcb.17.5.2920. PMC 232144. PMID 9111364.
• Wu L, Wu H, Ma L, Sangiorgi F, Wu N, Bell JR, Lyons GE, Maxson R (juli 1997). "Miz1, a novel zinc finger transcription factor that interacts with Msx2 and enhances its affinity for DNA". Mechanisms of Development. 65 (1–2): 3–17. doi:10.1016/S0925-4773(97)00032-4. PMID 9256341.
• Newberry EP, Latifi T, Battaile JT, Towler DA (august 1997). "Structure-function analysis of Msx2-mediated transcriptional suppression". Biochemistry. 36 (34): 10451–62. doi:10.1021/bi971008x. PMID 9265625.
• Stelnicki EJ, Kömüves LG, Holmes D, Clavin W, Harrison MR, Adzick NS, Largman C (oktobar 1997). "The human homeobox genes MSX-1, MSX-2, and MOX-1 are differentially expressed in the dermis and epidermis in fetal and adult skin". Differentiation; Research in Biological Diversity. 62 (1): 33–41. doi:10.1046/j.1432-0436.1997.6210033.x. PMID 9373945.
• Iimura T, Takeda K, Goseki M, Maruoka Y, Sasaki S, Oida S (1998). "Characterization of two length cDNA for human MSX-2 from dental pulp-derived cells". DNA Sequence. 8 (1–2): 87–92. doi:10.3109/10425179709020891. PMID 9522127.
• Newberry EP, Latifi T, Towler DA (august 1999). "The RRM domain of MINT, a novel Msx2 binding protein, recognizes and regulates the rat osteocalcin promoter". Biochemistry. 38 (33): 10678–90. doi:10.1021/bi990967j. PMID 10451362.
• Wilkie AO, Tang Z, Elanko N, Walsh S, Twigg SR, Hurst JA, Wall SA, Chrzanowska KH, Maxson RE (april 2000). "Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification". Nature Genetics. 24 (4): 387–90. doi:10.1038/74224. PMID 10742103. S2CID 21030594.
• Wuyts W, Reardon W, Preis S, Homfray T, Rasore-Quartino A, Christians H, Willems PJ, Van Hul W (maj 2000). "Identification of mutations in the MSX2 homeobox gene in families affected with foramina parietalia permagna". Human Molecular Genetics. 9 (8): 1251–5. doi:10.1093/hmg/9.8.1251. PMID 10767351.
• Quinn LM, Latham SE, Kalionis B (2000). "The homeobox genes MSX2 and MOX2 are candidates for regulating epithelial-mesenchymal cell interactions in the human placenta". Placenta. 21 Suppl A (Suppl A): S50-4. doi:10.1053/plac.1999.0514. PMID 10831122.
• Masuda Y, Sasaki A, Shibuya H, Ueno N, Ikeda K, Watanabe K (februar 2001). "Dlxin-1, a novel protein that binds Dlx5 and regulates its transcriptional function". The Journal of Biological Chemistry. 276 (7): 5331–8. doi:10.1074/jbc.M008590200. PMID 11084035.
• Shirakabe K, Terasawa K, Miyama K, Shibuya H, Nishida E (oktobar 2001). "Regulation of the activity of the transcription factor Runx2 by two homeobox proteins, Msx2 and Dlx5". Genes to Cells. 6 (10): 851–6. doi:10.1046/j.1365-2443.2001.00466.x. PMID 11683913. S2CID 22071040.

Vanjski linkovi

• GeneReviews/NCBI/UW/NIH entry on Enlarged Parietal Foramina/Cranium Bifidum
• MSX2 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)
• MSX2 lokacija ljudskog genoma UCSC Genome Browser.

MSX2 detalji ljudskog genoma u UCSC Genome Browser.

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.