Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prothymosin alpha, an immunoactive polypeptide of 12 kDa, has been isolated from porcine thymus, spleen, lung and kidney. It lacks aromatic and sulfur-containing amino acids and has a high content of glutamic and aspartic acids. Tryptic digestion of porcine thymus prothymosin alpha yielded peptides which on separation, amino acid analysis and alignment with the known sequence of prothymosin alpha from rat and man showed that the amino terminal portion of the molecule is conserved and the few differences present are confined to the carboxy terminal.
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PMID:Isolation and partial characterization of prothymosin alpha from porcine tissues. 338 98

Prothymosin alpha has been purified from human thymus and its amino acid sequence determined, except for a 15 amino acid segment including 10 glutamyl residues near the middle of the molecule. Like prothymosin alpha from rat thymus [A. A. Haritos, R. Blacher, S. Stein, J. Caldarella, and B. L. Horecker (1985) Proc. Natl. Acad. Sci. USA 82, 343-346], human prothymosin contains the thymosin alpha 1 sequence at its NH2-terminus. It contains a total of 109-110 residues compared to 111-112 for rat prothymosin alpha, with deletions corresponding to positions Gln39 and Lys108 of the rat polypeptide. Human prothymosin alpha also differs from rat prothymosin alpha at positions corresponding to residues 87, 92, and 102 of the latter, with substitutions of alanine for proline, alanine for valine, and aspartic acid for glutamic acid, respectively. Human prothymosin is significantly less active than rat prothymosin in protecting mice against infection with Candida albicans and in stimulating release in vivo of migration inhibitory factor. Thus, the differences in amino acid sequences, present mainly the COOH-terminal half of the polypeptides, may determine species specificity in biological properties.
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PMID:Human prothymosin alpha: amino acid sequence and immunologic properties. 353 56

The immunoregulatory polypeptide prothymosin alpha and its biologically active N-terminal fragment thymosin alpha 1m, with relative molecular masses of 12,500 and 3108 respectively, were found to behave as oligomers (trimers to hexamers) in gel-filtration measurements. This phenomenon of an apparent association of polypeptides has been reported for other thymosins--parathymosin alpha, thymosin beta 4 and thymosin beta 10. In contrast, sedimentation equilibrium ultracentrifugation shows that thymosin alpha 1 is a monomer with a relative molecular mass of 3000 +/- 200. Measurement of the diffusion coefficient as 221 micron2/s suggests that the molecule is approximately spherical. The implications for the molecular species of prothymosin alpha, parathymosin alpha, and beta-thymosins are discussed.
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PMID:On the molecular size of thymosins. 359 56

The primary structure of prothymosin alpha from rat thymus, containing 113 amino acid residues, is reported as follows: (formula; see text) The sequence of the first 28 amino acids at the NH2 terminus is identical to that of calf thymosin alpha 1. The dicarboxylic amino acids, which account for nearly half of the total residues in prothymosin alpha, are largely clustered in the central portion of the polypeptide chain. The polypeptide contains no aromatic or sulfur-containing amino acids. A computer analysis of the three-dimensional structure based on the primary sequence suggests that the molecule is composed of at least five alpha-helical regions interrupted by one short extended chain and three short random coils.
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PMID:Primary structure of rat thymus prothymosin alpha. 385 55

A polypeptide containing approximately equal to 112 amino acid residues, with the thymosin alpha 1 sequence at its NH2 terminus, has been isolated from rat thymus by using a radioimmunoassay with an antibody prepared against synthetic thymosin alpha 1. The new polypeptide, named "prothymosin alpha," was found to be the major substance crossreacting with thymosin alpha 1 antiserum in rat thymus extracts; peptides corresponding to thymosin alpha 1 or thymosin alpha 11 were not detected. In gel filtration at pH 2.8, prothymosin alpha emerged as a single symmetrical peak corresponding to an apparent molecular weight of 32,000, approximately 3 times larger than the minimum molecular weight calculated from its amino acid composition. On the same gel filtration columns, synthetic thymosin alpha 1 (calculated Mr = 3108) emerged at a position corresponding to a molecular weight of 10,000-11,000. Thus, both prothymosin alpha and thymosin alpha 1 appear to exist in solution as oligomers, possibly as trimers. Prothymosin alpha and synthetic thymosin alpha 1 also were separated readily in reverse-phase HPLC and in isoelectric focusing; the isoelectric point of prothymosin alpha determined by the latter procedure was found to be 3.55, consistent with an unusually high content of glutamic and aspartic acids based on amino acid analyses. Prothymosin alpha appears to represent the native polypeptide from which thymosin alpha 1 and other fragments are generated during the isolation of thymosin fraction 5.
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PMID:Prothymosin alpha: isolation and properties of the major immunoreactive form of thymosin alpha 1 in rat thymus. 658 93

A radioimmunoassay specific for the C-terminus of human prothymosin alpha was developed using the synthetic peptide [Cys-Aca degrees]-human prothymosin alpha (90-109)-OH coupled to KLH as antigen and the analogue [Tyr-Aca degrees]-human prothymosin alpha (90-109)-OH labelled with 125I as tracer. The radioimmunoassay measured intact prothymosin alpha, in the range of 2-100 pmol and does not cross-react with the partly homologous polypeptide parathymosin alpha. A major epitope was located in the segment 95-107. A radioimmunoassay specific for the N-terminus of human parathymosin alpha, also measuring intact parathymosin alpha in the range of 1-20 pmol and not cross-reacting with prothymosin alpha, was developed using the synthetic peptide [Cys-Aca degrees]-human parathymosin alpha (1-30)-OH as antigen coupled to KLH and the analogue [Tyr-Aca degrees]-human parathymosin alpha (1-10)-OH labelled with 125I as tracer. A major epitope was located in the segment 1-10. These radioimmunoassays, together with a previously established radioimmunoassay for the N-terminus of prothymosin alpha, permitted the identification of the molecular forms of the cross-reactive materials in both normal and neoplastic breast tissue extracts as intact prothymosin alpha and parathymosin alpha. It was also possible to reveal significantly higher levels of both alpha-thymosins in breast cancer tissue compared to the nearby healthy tissue--the mean of 14 samples was over 14-fold higher--suggesting a role of both prothymosin alpha and parathymosin alpha in cell proliferation. The reported radioimmunoassays are expected to facilitate the search for prognostic and/or diagnostic applications of these polypeptides in human cancer.
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PMID:Radioimmunoassays for the C-terminus of prothymosin alpha and the N-terminus of parathymosin alpha for the measurement of the levels of alpha-thymosins in human cancer. 751 Jul 58

Prothymosin alpha is a widely distributed polypeptide whose function, though unknown, seems to be related to cell proliferation. In vitro, it is a substrate for casein kinase-2. In this work, extracts of mitogenically stimulated murine splenic lymphocytes labeled with [32P] orthophosphate were found to contain [32P]prothymosin alpha. Phosphorylation activity was highly dependent on mitogenic activation with concanavalin A plus interleukin-2. While cells remained viable, phosphorylation increased with stimulation time in the presence of [32P]orthophosphate. Structural analysis showed that prothymosin alpha was phosphorylated at Thr residues located among its first 14 amino acids, whereas its in vitro phosphorylation by casein kinase-2 affects both Ser and Thr residues in this fragment, apparently in similar proportions. Thus, casein kinase-2 seems not to be responsible for the phosphorylation of prothymosin alpha in vivo. Prothymosin alpha was also found to be phosphorylated in proliferating murine thymocytes and HeLa cells; the phosphorylation sites were the same as in splenic lymphocytes, but the rate of phosphorylation was about 5 times lower. In thymocytes and subconfluent HeLa cells, the [32P]prothymosin alpha concentrations of the cytosolic and nuclear fractions were similar; in splenic lymphocytes, [32P]prothymosin alpha was found mostly in cytosol.
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PMID:Prothymosin alpha is phosphorylated in proliferating stimulated cells. 844 45

The important immunological activities of Thymosin alpha 1 (T alpha 1), a peptide derived from the thymus, led to its use in combination therapies in cancer patients. Prothymosin alpha (ProT alpha) is a highly acidic polypeptide, first isolated as the putative precursor of T alpha 1. However ProT alpha is now known to be more immunoreactive than T alpha 1 in certain in vivo and in vitro assays. Recent results indicate that ProT alpha may be useful to design future therapeutic interventions in cancer patients if the mechanisms underlying these effects are puzzled out. With this in mind, we radiolabeled ProT alpha to obtain a high specific activity and a high biological activity for 125I-ProT alpha. Moreover, we also obtained autoantibodies exhibiting high titers and an unique specificity for anti-ProT alpha and anti-T alpha 1. With both tools we studied the presence of binding sites for ProT alpha on the surface of lymphoblast cells. We conclude that ProT alpha binds through the non-T alpha 1 sequence.
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PMID:Binding of 125I-prothymosin alpha to lymphoblasts through the non-thymosin alpha 1 sequence. 863

Prothymosin alpha (Pro Talpha) is a polypeptide which appears to be involved in cell proliferation, though its precise function has yet to be identified. Here, we report experiments which show that calf Pro Talpha selectively binds to core histones and histone H1 in vitro. Characterization of these interactions by various procedures (including affinity chromatography on Pro T alpha-Sepharose columns, immunoblotting assay and investigation of the behaviour of mixtures of Pro T alpha and histones in solution) indicated that Pro T alpha has higher affinity for core histones (particularly H3 and H4) than for H1. Similarities between the histone-binding patterns of Pro T alpha and of poly(glutamic acid) suggest that the observed histone-binding capacity resides largely in the acidic central region of Pro T alpha. However, all five histones were also bound by T alpha 1 (a peptide corresponding to the first 28 amino acids of Pro T alpha); histone binding by the N-terminal region of Pro T alpha thus cannot be ruled out. Phosphorylation of Pro T alpha does not appear to affect these interactions. In accordance with the observed capacity for histone binding, Pro T alpha (in conjunction with ATP and some Pro T alpha-binding factor/s in a thymocyte extract) was able to induce in vitro nucleosome assembly. We discuss the possibility that Pro T alpha plays a role in chromatin remodelling.
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PMID:Prothymosin alpha binds histones in vitro and shows activity in nucleosome assembly assay. 881 29

Our study examines the effect of apoptosis on prothymosin alpha, an abundant, nuclear protein intimately involved with proliferation of all mammalian cells. When HeLa cells were treated with actinomycin D, with etoposide, or with staurosporine following synchronization with hydroxyurea, they underwent apoptosis based on several specific criteria, including fragmentation of DNA and activation of specific caspases. Similarly treated NIH3T3 cells arrested and displayed no indicators of apoptosis. In HeLa, but not in NIH3T3 cells, prothymosin alpha levels declined precipitously and a truncated version of the protein was formed. The following observations implicate caspase activity: (1) The truncated polypeptide arose only in the treated HeLa cell cultures. (2) The appearance of the truncated polypeptide coincided with the activation of caspase 3 and the cleavage of poly(ADP-ribose) polymerase, a known caspase substrate. (3) Carbobenzoxy-DEVD-fluoromethylketone, a cell-permeable caspase 3 inhibitor, blocked cleavage and degradation of prothymosin alpha. (4) The same inhibitor, when added to mixed extracts of apoptotic and normal cells, prevented cleavage of intact prothymosin alpha. (5) Recombinant caspase 3 and, to a much lesser extent, caspase 7 truncated purified prothymosin alpha. (6) In HeLa cells, cleavage occurred at three overlapping caspase 3-like sites with the consensus sequence D-X-X-D and released 10 to 14 residues from the carboxyl terminus, including the core nuclear localization signal. Two immediate consequences of the cleavage were observed: truncated prothymosin alpha was no longer confined to the nucleus and it was deficient in phosphate. These data suggest that the disabling of prothymosin alpha is a significant event in apoptosis. J. Cell. Physiol. 182:256-268, 2000. Published 2000 Wiley-Liss, Inc.
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PMID:Functional discontinuities in prothymosin alpha caused by caspase cleavage in apoptotic cells. 1062 90


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