Thymosin beta-4

TMSB4X
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 3TU5, 4PL7, 4PL8
Identifiers
Aliases	TMSB4X, FX, PTMB4, TB4X, TMSB4, thymosin beta 4, X-linked
External IDs	GeneCards: TMSB4X
Gene ontology Molecular function • actin binding • poly(A) RNA binding • actin monomer binding • protein binding Cellular component • cytoplasm • extracellular region • cytosol • cytoskeleton • platelet alpha granule lumen • nucleus Biological process • platelet degranulation • regulation of cell migration • osteoblast differentiation • actin filament organization Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7114	n/a
Ensembl	ENSG00000205542	n/a
UniProt	P62328	n/a
RefSeq (mRNA)	NM_021109	n/a
RefSeq (protein)	NP_066932.1	n/a
Location (UCSC)	Chr X: 12.98 – 12.98 Mb	n/a
PubMed search	[1]	n/a
Wikidata

View/Edit Human

Thymosin beta-4 is a protein that in humans is encoded by the TMSB4X gene.^[2][3][4]

The protein consists (in humans) of 43 amino acids and has a molecular weight of 4921 g/mol.^[5]

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).^[4]

Clinical significance

It has been studied in a number of clinical trials.^[6]

The thymosin beta-4 peptide, if used after a heart attack, might reactivate cardiac progenitor cells to repair damaged heart tissue.^[7][8]

Doping in Sports

Thymosin beta-4 was allegedly used by some players in various Australian football codes and is under investigation by the Australian Sports Anti-Doping Authority for anti-doping violations.^[9][10]

On 30 March 2015, the Australian Football League anti-doping tribunal initially cleared players of the Essendon Football Club over the use of thymosin beta-4, however after an appeal by the World Anti-Doping Agency, this was overturned on 12 January 2016.^[11]

Interactions

TMSB4X has been shown to interact with ACTA1^[12][13] and ACTG1.^[14][15]

See also

• Beta thymosins
• Thymosin beta-4, Y-chromosomal
• Thymosins

References

1. "Human PubMed Reference:".
2. Gómez-Márquez J, Dosil M, Segade F, Bustelo XR, Pichel JG, Dominguez F, Freire M (Oct 1989). "Thymosin-beta 4 gene. Preliminary characterization and expression in tissues, thymic cells, and lymphocytes". Journal of Immunology. 143 (8): 2740–4. PMID 2677145.
3. Lahn BT, Page DC (Oct 1997). "Functional coherence of the human Y chromosome". Science. 278 (5338): 675–80. Bibcode:1997Sci...278..675L. doi:10.1126/science.278.5338.675. PMID 9381176.
4. "Entrez Gene: TMSB4X thymosin, beta 4, X-linked".
5. "protein NP_066932". NCBI.
6. Crockford D, Turjman N, Allan C, Angel J (Apr 2010). "Thymosin beta4: structure, function, and biological properties supporting current and future clinical applications". Annals of the New York Academy of Sciences. 1194: 179–89. Bibcode:2010NYASA1194..179C. doi:10.1111/j.1749-6632.2010.05492.x. PMID 20536467.
7. Smart N, Bollini S, Dubé KN, Vieira JM, Zhou B, Davidson S, Yellon D, Riegler J, Price AN, Lythgoe MF, Pu WT, Riley PR (Jun 2011). "De novo cardiomyocytes from within the activated adult heart after injury". Nature. 474 (7353): 640–4. doi:10.1038/nature10188. PMC 3696525. PMID 21654746. Lay summary – BBC News.
8. British Heart Foundation. "Regenerative science: Mending Broken Hearts". YouTube Video.
9. Koh B. "Cronulla Sharks and thymosin beta-4 … is it doping?". The Conversation.
10. Ho EN, Kwok WH, Lau MY, Wong AS, Wan TS, Lam KK, Schiff PJ, Stewart BD (Nov 2012). "Doping control analysis of TB-500, a synthetic version of an active region of thymosin β₄, in equine urine and plasma by liquid chromatography-mass spectrometry". Journal of Chromatography A. 1265: 57–69. doi:10.1016/j.chroma.2012.09.043. PMID 23084823.
11. "Essendon supplements saga: ASADA backs Court of Arbitration for Sport decision to upheld WADA appeal". ABC News (Australian Broadcasting Corporation).
12. Ballweber E, Hannappel E, Huff T, Stephan H, Haener M, Taschner N, Stoffler D, Aebi U, Mannherz HG (Jan 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". Journal of Molecular Biology. 315 (4): 613–25. doi:10.1006/jmbi.2001.5281. PMID 11812134.
13. 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.
14. 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.
15. Van Troys M, Dewitte D, Goethals M, Carlier MF, Vandekerckhove J, Ampe C (Jan 1996). "The actin binding site of thymosin beta 4 mapped by mutational analysis". The EMBO Journal. 15 (2): 201–10. PMC 449934. PMID 8617195.

Further reading

• Huff T, Müller CS, Otto AM, Netzker R, Hannappel E (Mar 2001). "beta-Thymosins, small acidic peptides with multiple functions". The International Journal of Biochemistry & Cell Biology. 33 (3): 205–20. doi:10.1016/S1357-2725(00)00087-X. PMID 11311852.
• Bubb MR (2003). "Thymosin beta 4 interactions". Vitamins and Hormones. 66: 297–316. doi:10.1016/S0083-6729(03)01008-2. PMID 12852258.
• Goldschmidt-Clermont PJ, Furman MI, Wachsstock D, Safer D, Nachmias VT, Pollard TD (Sep 1992). "The control of actin nucleotide exchange by thymosin beta 4 and profilin. A potential regulatory mechanism for actin polymerization in cells". Molecular Biology of the Cell. 3 (9): 1015–24. doi:10.1091/mbc.3.9.1015. PMC 275662. PMID 1330091.
• Sanders MC, Goldstein AL, Wang YL (May 1992). "Thymosin beta 4 (Fx peptide) is a potent regulator of actin polymerization in living cells". Proceedings of the National Academy of Sciences of the United States of America. 89 (10): 4678–82. Bibcode:1992PNAS...89.4678S. doi:10.1073/pnas.89.10.4678. PMC 49146. PMID 1584803.
• Safer D, Elzinga M, Nachmias VT (Mar 1991). "Thymosin beta 4 and Fx, an actin-sequestering peptide, are indistinguishable". The Journal of Biological Chemistry. 266 (7): 4029–32. PMID 1999398.
• Clauss IM, Wathelet MG, Szpirer J, Islam MQ, Levan G, Szpirer C, Huez GA (Jan 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, Gatanaga T, Shibai H, Morioka H, Andoh T (Oct 1985). "Detection of a countertranscript in promyelocytic leukemia cells HL60 during early differentiation by TPA". Biochemical and Biophysical Research Communications. 132 (1): 100–9. doi:10.1016/0006-291X(85)90994-5. PMID 2998351.
• Gondo H, Kudo J, White JW, Barr C, Selvanayagam P, Saunders GF (Dec 1987). "Differential expression of the human thymosin-beta 4 gene in lymphocytes, macrophages, and granulocytes". Journal of Immunology. 139 (11): 3840–8. PMID 3500230.
• Friedman RL, Manly SP, McMahon M, Kerr IM, Stark GR (Oct 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 (Mar 1983). "Distribution of thymosin beta 4 in vertebrate classes". Archives of Biochemistry and Biophysics. 221 (2): 570–6. doi:10.1016/0003-9861(83)90177-7. PMID 6838210.
• Pantaloni D, Carlier MF (Dec 1993). "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, Carlier MF, Vandekerckhove J, Ampe C (Jan 1996). "The actin binding site of thymosin beta 4 mapped by mutational analysis". The EMBO Journal. 15 (2): 201–10. PMC 449934. PMID 8617195.
• Feinberg J, Heitz F, Benyamin Y, Roustan C (May 1996). "The N-terminal sequences (5-20) of thymosin beta 4 binds to monomeric actin in an alpha-helical conformation". Biochemical and Biophysical Research Communications. 222 (1): 127–32. doi:10.1006/bbrc.1996.0709. PMID 8630056.
• 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.
• Malinda KM, Goldstein AL, Kleinman HK (May 1997). "Thymosin beta 4 stimulates directional migration of human umbilical vein endothelial cells". FASEB Journal. 11 (6): 474–81. PMID 9194528.
• Chen J, Peterson RT, Schreiber SL (Jun 1998). "Alpha 4 associates with protein phosphatases 2A, 4, and 6". Biochemical and Biophysical Research Communications. 247 (3): 827–32. doi:10.1006/bbrc.1998.8792. PMID 9647778.
• Huff T, Ballweber E, Humeny A, Bonk T, Becker C, Müller CS, Mannherz HG, Hannappel E (Dec 1999). "Thymosin beta(4) serves as a glutaminyl substrate of transglutaminase. Labeling with fluorescent dansylcadaverine does not abolish interaction with G-actin". FEBS Letters. 464 (1-2): 14–20. doi:10.1016/S0014-5793(99)01670-1. PMID 10611475.
• De La Cruz EM, Ostap EM, Brundage RA, Reddy KS, Sweeney HL, Safer D (May 2000). "Thymosin-beta(4) changes the conformation and dynamics of actin monomers". Biophysical Journal. 78 (5): 2516–27. Bibcode:2000BpJ....78.2516D. doi:10.1016/S0006-3495(00)76797-X. PMC 1300842. PMID 10777749.