Thymosin beta-4
Thymosin beta-4 is a protein that in humans is encoded by the TMSB4X gene.[1][2][3]
The protein consists (in humans) of 44 amino acids (msdkpdmaei ekfdksklkk tetqeknplp sketieqekq ages) molWt 4921.[4]
Function
This gene encodes an actin sequestering protein which plays a role in regulation of actin polymerization. The protein is also involved in cell proliferation, migration, and differentiation. This gene escapes X inactivation and has a homolog on chromosome Y (TMSB4Y).[3]
Clinical significance
It has been studied in a number of clinical trials.[5]
The thymosin beta-4 peptide, if used after a heart attack, might reactivate cardiac progenitor cells to repair damaged heart tissue.[6][7]
Interactions
TMSB4X has been shown to interact with ACTA1[8][9] and ACTG1.[10][11]
See also
References
- ^ Gomez-Marquez J, Dosil M, Segade F, Bustelo XR, Pichel JG, Dominguez F, Freire M (Nov 1989). "Thymosin-beta 4 gene. Preliminary characterization and expression in tissues, thymic cells, and lymphocytes". J Immunol 143 (8): 2740–4. PMID 2677145.
- ^ Lahn BT, Page DC (Nov 1997). "Functional coherence of the human Y chromosome". Science 278 (5338): 675–80. doi:10.1126/science.278.5338.675. PMID 9381176.
- ^ a b "Entrez Gene: TMSB4X thymosin, beta 4, X-linked". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7114.
- ^ http://www.ncbi.nlm.nih.gov/protein/NP_066932
- ^ Crockford D, Turjman N, Allan C, Angel J (April 2010). "Thymosin beta4: structure, function, and biological properties supporting current and future clinical applications". Ann. N. Y. Acad. Sci. 1194: 179–89. doi:10.1111/j.1749-6632.2010.05492.x. PMID 20536467.
- ^ Smart N, Bollini D, Dubé KN, Vieira JM, Zhou B, Davidson S, Yellon D, Riegler J, Price AN, Lythgoe MF, Pu WT, Riley PR (June 2011). "De novo cardiomyocytes from within the activated adult heart after injury". Nature 474 (7353). doi:10.1038/nature10188. PMID 21654746. Lay summary – BBC News.
- ^ Regenerative science - British Heart Foundation Mending Broken Hearts YouTube Video
- ^ Ballweber E, Hannappel E, Huff T, Stephan H, Haener M, Taschner N, Stoffler D, Aebi U, Mannherz HG (January 2002). "Polymerisation of chemically cross-linked actin:thymosin beta(4) complex to filamentous actin: alteration in helical parameters and visualisation of thymosin beta(4) binding on F-actin". J. Mol. Biol. 315 (4): 613–25. doi:10.1006/jmbi.2001.5281. PMID 11812134.
- ^ Safer D, Sosnick TR, Elzinga M (May 1997). "Thymosin beta 4 binds actin in an extended conformation and contacts both the barbed and pointed ends". Biochemistry 36 (19): 5806–16. doi:10.1021/bi970185v. PMID 9153421.
- ^ Hertzog M, van Heijenoort C, Didry D, Gaudier M, Coutant J, Gigant B, Didelot G, Préat T, Knossow M, Guittet E, Carlier MF (May 2004). "The beta-thymosin/WH2 domain; structural basis for the switch from inhibition to promotion of actin assembly". Cell 117 (5): 611–23. doi:10.1016/S0092-8674(04)00403-9. PMID 15163409.
- ^ Van Troys M, Dewitte D, Goethals M, Carlier MF, Vandekerckhove J, Ampe C (January 1996). "The actin binding site of thymosin beta 4 mapped by mutational analysis". EMBO J. 15 (2): 201–10. PMC 449934. PMID 8617195. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=449934.
Further reading
- Huff T, Müller CS, Otto AM, et al. (2001). "beta-Thymosins, small acidic peptides with multiple functions.". Int. J. Biochem. Cell Biol. 33 (3): 205–20. doi:10.1016/S1357-2725(00)00087-X. PMID 11311852.
- Bubb MR (2003). "Thymosin beta 4 interactions.". Vitam. Horm. 66: 297–316. doi:10.1016/S0083-6729(03)01008-2. PMID 12852258.
- Goldschmidt-Clermont PJ, Furman MI, Wachsstock D, et al. (1992). "The control of actin nucleotide exchange by thymosin beta 4 and profilin. A potential regulatory mechanism for actin polymerization in cells.". Mol. Biol. Cell 3 (9): 1015–24. PMC 275662. PMID 1330091. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=275662.
- Sanders MC, Goldstein AL, Wang YL (1992). "Thymosin beta 4 (Fx peptide) is a potent regulator of actin polymerization in living cells.". Proc. Natl. Acad. Sci. U.S.A. 89 (10): 4678–82. doi:10.1073/pnas.89.10.4678. PMC 49146. PMID 1584803. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=49146.
- Safer D, Elzinga M, Nachmias VT (1991). "Thymosin beta 4 and Fx, an actin-sequestering peptide, are indistinguishable.". J. Biol. Chem. 266 (7): 4029–32. PMID 1999398.
- Clauss IM, Wathelet MG, Szpirer J, et al. (1991). "Human thymosin-beta 4/6-26 gene is part of a multigene family composed of seven members located on seven different chromosomes.". Genomics 9 (1): 174–80. doi:10.1016/0888-7543(91)90236-8. PMID 2004759.
- Soma G, Murata M, Kitahara N, et al. (1985). "Detection of a countertranscript in promyelocytic leukemia cells HL60 during early differentiation by TPA.". Biochem. Biophys. Res. Commun. 132 (1): 100–9. doi:10.1016/0006-291X(85)90994-5. PMID 2998351.
- Gondo H, Kudo J, White JW, et al. (1988). "Differential expression of the human thymosin-beta 4 gene in lymphocytes, macrophages, and granulocytes.". J. Immunol. 139 (11): 3840–8. PMID 3500230.
- Friedman RL, Manly SP, McMahon M, et al. (1984). "Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells.". Cell 38 (3): 745–55. doi:10.1016/0092-8674(84)90270-8. PMID 6548414.
- Erickson-Viitanen S, Ruggieri S, Natalini P, Horecker BL (1983). "Distribution of thymosin beta 4 in vertebrate classes.". Arch. Biochem. Biophys. 221 (2): 570–6. doi:10.1016/0003-9861(83)90177-7. PMID 6838210.
- Pantaloni D, Carlier MF (1994). "How profilin promotes actin filament assembly in the presence of thymosin beta 4.". Cell 75 (5): 1007–14. doi:10.1016/0092-8674(93)90544-Z. PMID 8252614.
- Van Troys M, Dewitte D, Goethals M, et al. (1996). "The actin binding site of thymosin beta 4 mapped by mutational analysis.". EMBO J. 15 (2): 201–10. PMC 449934. PMID 8617195. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=449934.
- Feinberg J, Heitz F, Benyamin Y, Roustan C (1996). "The N-terminal sequences (5-20) of thymosin beta 4 binds to monomeric actin in an alpha-helical conformation.". Biochem. Biophys. Res. Commun. 222 (1): 127–32. doi:10.1006/bbrc.1996.0709. PMID 8630056.
- Safer D, Sosnick TR, Elzinga M (1997). "Thymosin beta 4 binds actin in an extended conformation and contacts both the barbed and pointed ends.". Biochemistry 36 (19): 5806–16. doi:10.1021/bi970185v. PMID 9153421.
- Malinda KM, Goldstein AL, Kleinman HK (1997). "Thymosin beta 4 stimulates directional migration of human umbilical vein endothelial cells.". FASEB J. 11 (6): 474–81. PMID 9194528.
- Chen J, Peterson RT, Schreiber SL (1998). "Alpha 4 associates with protein phosphatases 2A, 4, and 6.". Biochem. Biophys. Res. Commun. 247 (3): 827–32. doi:10.1006/bbrc.1998.8792. PMID 9647778.
- Huff T, Ballweber E, Humeny A, et al. (2000). "Thymosin beta(4) serves as a glutaminyl substrate of transglutaminase. Labeling with fluorescent dansylcadaverine does not abolish interaction with G-actin.". FEBS Lett. 464 (1-2): 14–20. doi:10.1016/S0014-5793(99)01670-1. PMID 10611475.
- De La Cruz EM, Ostap EM, Brundage RA, et al. (2000). "Thymosin-beta(4) changes the conformation and dynamics of actin monomers.". Biophys. J. 78 (5): 2516–27. Bibcode 2000BpJ....78.2516D. doi:10.1016/S0006-3495(00)76797-X. PMC 1300842. PMID 10777749. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1300842.