Molecular cloning of Ian4: A BCR/ABL-induced gene that encodes an outer membrane mitochondrial protein with GTP-binding activity

Abstract

Using the representation difference analysis technique, we have identified a novel gene, lan4, which is preferentially expressed in hematopoietic precursor 32D cells transfected with wild-type versus mutant forms of the Bcr/Abl oncogene. lan4 expression was undetectable in 32D cells transfected with v-src, oncogenic Ha-ras or v-Abl. Murine lan4 maps to chromosome 6, 25 cM from the centromere. The lan4 mRNA contains two open reading frames (ORFs) separated by 5 nt. The first ORF has the potential to encode for a polypeptide of 67 amino acids without apparent homology to known proteins. The second ORF encodes a protein of 301 amino acids with a GTP/ATP-binding site in the N-terminus and a hydrophobic domain in the extreme C-terminus. The IAN-4 protein resides in the mitochondrial outer membrane and the last 20 amino acids are necessary for this localization. The IAN-4 protein has GTP-binding activity and shares sequence homology with a novel family of putative GTP-binding proteins: the immuno-associated nucleotide (IAN) family.