STRUCTURE AND MAPPING OF THE HUMAN THYMOPOIETIN (TMPO) GENE AND RELATIONSHIP OF HUMAN TMPO-BETA TO RAT LAMIN-ASSOCIATED POLYPEPTIDE-2

Thymopoietins (TMPOs, previously abbreviated TPs) alpha (75 kDa), beta (51 kDa), and gamma (39 kDa) are related nuclear proteins expressed i n many or all tissues. TMPO alpha is present diffusely throughout the nucleus, while TMPOs beta and gamma are localized to the nuclear membr ane. Here we report the cloning and analysis of a single TMPO gene enc oding TMPOs alpha, beta, and gamma, which are produced by alternative mRNA splicing, as previously inferred from cDNA sequences. The eight e xons of the TMPO gene are spread over similar to 35 kb. Exon 4, which is spliced into TMPO alpha mRNA, contains sequences that encode a puta tive basic nuclear localization motif. Exon 8, which is spliced into T MPO beta and gamma mRNAs, encodes a hydrophobic putative membrane-span ning domain that is thought to target TMPOs beta and gamma to the nucl ear membrane. TMPO beta appears to be the human homologue of the recen tly described rat protein LAPS (lamina-associated polypeptide 2), whic h is thought to play an important role in the regulation of nuclear ar chitecture by binding lamin B1 and chromosomes in a manner regulated b y phosphorylation during mitosis (K. Furukawa and L. Gerace, La Jolla, pers. comm., 22 Nov. 1994). The human TMPO gene maps to chromosome ba nd 12q22. (C) 1995 Academic Press, Inc.