Thymosin beta-4

Thymosin beta 4, X-linked
Available structures PDB Human UniProt search: PDBe, RCSB List of PDB id codes 1UY5​, 3TU5​, 4PL7​, 4PL8​
Identifiers
Symbols	TMSB4X ; FX; PTMB4; TB4X; TMSB4
External IDs	OMIM: 300159 GeneCards: TMSB4X Gene
Gene ontology Molecular function • actin monomer binding • protein binding • poly(A) RNA binding Cellular component • extracellular region • cytoskeleton • platelet alpha granule lumen Biological process • platelet degranulation • actin filament organization • blood coagulation • platelet activation • sequestering of actin monomers 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	n/a
Location (UCSC)	Chr X: 12.98 – 12.98 Mb	n/a
PubMed search		n/a

Thymosin beta-4 is a protein that in humans is encoded by the TMSB4X gene.^[1][2][3]

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

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 ^[8][9]

Players of the Essendon Football Club were cleared of use of Thymosin Beta 4 on March 30, 2015 by the Australian Football League anti-doping tribunal, however after an appeal by the World Anti-Doping Agency, this was overturned on the January 12, 2016.^[10]

Interactions

TMSB4X has been shown to interact with ACTA1^[11][12] and ACTG1.^[13][14]

See also

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

References

1. 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.
2. 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.
3. "Entrez Gene: TMSB4X thymosin, beta 4, X-linked".
4. "protein NP_066932". NCBI.
5. 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.
6. 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.
7. British Heart Foundation. "Regenerative science: Mending Broken Hearts". YouTube Video.
8. Koh B. "Cronulla Sharks and thymosin beta-4 … is it doping?". The Conversation.
9. 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.
10. "Essendon supplements saga: ASADA backs Court of Arbitration for Sport decision to upheld WADA appeal". ABC News (Australian Broadcasting Corporation).
11. 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.
12. 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.
13. 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.
14. 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.