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

Using the representation difference analysis technique, We have identified a novel gene, Ian4, which is preferentially expressed in hematopoietic prec ursor 32D cells transfected with wild-type versus mutant forms of the Bcr/A bl oncogene, Ian4 expression was undetectable in 32D cells transfected with v-src, oncogenic Ha-ras or v-Abl, Murine Ian4 maps to chromosome 6, 25 cM from the centromere, The Ian4 mRNA-contains two open reading frames (ORFs) separated by 5 nt, The first ORF has the potential to encode for a polypept ide of 67 amino acids without apparent homology to known proteins. The seco nd ORF encodes a protein of 301 amino acids with a GTP/ATB-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-bindi ng activity and shares sequence homology with a novel family of putative GT P-binding proteins: the immuno-associated -nucleotide (IAN) family.