The study shows that the gene for prothymosin alpha, which contains the thymosin‑alpha‑1 fragment, is highly variable and gets turned on when cells are stimulated to grow. Thymosin‑alpha‑1 is just a piece of this larger protein and isn’t secreted outside the cell, suggesting its main role is inside cells during proliferation.

Clones for human prothymosin alpha have been identified in cDNA libraries from staphylococcal enterotoxin A-stimulated normal human lymphocytes and from simian virus 40-transformed fibroblasts. The 1198-base-pair fibroblast clone has been sequenced. The encoded protein is highly acidic (54 residues out of 111) and shares greater than 90% sequence homology with rat prothymosin alpha. The peptide "hormone" thymosin alpha 1 appears at positions 2-29 of the prothymosin alpha amino acid sequence. There is no N-terminal signal peptide. Examination of mouse and human tissues revealed the presence of prothymosin alpha mRNA in kidney, liver, spleen, normal lymphocytes (predominantly T cells), human T-cell leukemia virus-infected T cells, and myeloma cells (B-cell lineage). Prothymosin alpha mRNA is inducible; upon mitogen stimulation it increased greater than 15-fold above the level found in resting lymphocytes. Similarly, serum-deprived NIH 3T3 cells responded to serum restitution with an increase in prothymosin alpha mRNA. Characterization of human genomic DNA by Southern blot analysis disclosed a complicated pattern consistent with genetic polymorphism. These data suggest that prothymosin alpha plays an intracellular role tied to cell proliferation. There is no evidence that it serves as a precursor for secreted thymic peptides. However, given the complexity at the genomic level, multiple functions, including a putative secretory capability, cannot be excluded.