Molecular characterization of KLHL3, a human homologue of the Drosophila kelch gene

The Drosophila kelch protein is a structural component of ring canals and i s required for oocyte maturation. Here, we report the cloning and genomic s tructure of a new human homologue of kelch, KLHL3. At the amino acid level, KLHL3 shares 77% similarity with Drosophila kelch and 89% similarity with Mayven (KLHL2), another human kelch homolog. The similar to 6.5-kb mRNA has a single open reading frame encoding a protein of 587 amino acids with a p redicted molecular mass of 650 kDa. Like kelch and KLHL2, the KLHL3 protein contains a poxvirus and zinc finger domain at the N-terminus and six tande m repeats (kelch repeats) at the C-terminus. At least three isoforms, which differ in the length of the N-terminus, are produced and may be the result of alternative promoter usage. We also identified alternative polyadenylat ion sites and alternative splicing; thus, as many as 12 mRNA variants and s ix putative protein isoforms could be produced, The KLHL3 gene is mapped to human chromosome 5, band q31, contains 17 exons, and spans similar to 120 kb of genomic DNA. KLHL3 maps within the smallest commonly deleted segment in myeloid leukemias characterized by a deletion of 5q; however, we detecte d no inactivating mutations of KLHL3 in malignant myeloid disorders with lo ss of 5q. (C) 2000 Academic Press.