Structure and Mapping of the Human Thymopoietin (TMPO) Gene and Relationship of Human TMPO Β to Rat Lamin-Associated Polypeptide 2

Thymopoietins (TMPOs, previously abbreviated TPs) α (75 kDa), β (51 kDa), and γ (39 kDa) are related nuclear proteins expressed in many or all tissues. TMPO α is present diffusely throughout the nucleus, while TMPOs β and γ are localized to the nuclear membrane. Here we report the cloning and analysis of a single TMPO gene encoding TMPOs α, β, and γ, which are produced by alternative mRNA splicing, as previously inferred from cDNA sequences. The eight exons of the TMPO gene are spread over ∼35 kb. Exon 4, which is spliced into TMPO α mRNA, contains sequences that encode a putative basic nuclear localization motif. Exon 8, which is spliced into TMPO β and γ mRNAs, encodes a hydrophobic putative membranespanning domain that is thought to target TMPOs β and γ to the nuclear membrane. TMPO β appears to be the human homologue of the recently described rat protein LAP2 (lamina-associated polypeptide 2), which is thought to play an important role in the regulation of nuclear architecture by binding lamin B1 and chromosomes in a manner regulated by phosphorylation during mitosis (K. Furukawa and L. Gerace, La Jolla, pers. comm., 22 Nov. 1994). The human TMPO gene maps to chromosome band 12q22

Three distinct human thymopoietins are derived from alternatively spliced mRNAs.

Thymopoietin (TP) was originally isolated as a 5-kDa 49-aa protein from bovine thymus in studies of the effects of thymic extracts on neuromuscular transmission and was subsequently observed to affect T-cell differentiation and function. We now report the isolation of cDNA clones for three alternatively spliced mRNAs that encode three distinct human T-cell TPs. Proteins encoded by these mRNAs, which we have named TP alpha (75 kDa), TP beta (51 kDa), and TP gamma (39 kDa), contain identical N-terminal regions, including sequences nearly identical to that of the originally isolated 49-aa protein, but divergent C-terminal regions. TP mRNAs are expressed in many tissues, most abundantly in adult thymus and fetal liver of the tissues so far examined. Distinct structural domains and functional motifs in TPs alpha, beta, and gamma suggest that the proteins have unique functions and may be directed to distinct subcellular compartments