Nrh, a human homologue of Nr-13 associates with Bcl-Xs and is an inhibitorof apoptosis

In search of human homologues of the anti-apoptotic protein Nr-13, we have characterized a human EST clone that potentially encodes a protein, which i s the closest homologue of Nr-13 among the Bcl-2 family members, to date kn own, in humans. Phylogenetic analyses suggest Human nrh, Mouse diva/boo and Quail nr-13 to be orthologous genes. The nrh gene has the same overall org anization as nr-13 and diva/boo with one single intron interrupting the ORF at the level of the Bcl-2-homology domain BH2. RT-PCR-based analysis of nr h expression indicated that this gene is preferentially expressed in the lu ngs, the liver and the kidneys. Interestingly, two in frame ATG codons can lead potentially to the synthesis of two products, one of them lacking 10 a minoacids at the N-terminal end. Sequence alignment with nr-13 and Diva/Boo in addition to secondary structure prediction of the nrh transcript sugges ted that the shortest protein will be preferentially synthetized. Immunohis tochemical analyses have revealed that Nrh is associated with mitochondria and the nuclear envelope. Moreover, Nrh preferentially associates with the apoptosis accelerator Bcl-Xs and behaves as an inhibitor of apoptosis both in yeast and vertebrate cells.