beta-Catenin, I kappa B alpha, and HIV Vpu are recruited to the ubiquitin-proteasome degradation pathway by beta TRCP, one of the components of the ubiquitin ligase complex. beta TRCP2, a related gene of beta TRCP, was cloned and characterized. Three isoforms, beta TRCP2A, beta TRCP2B, and beta TRCP2C, were identified. All of these beta TRCP2 isoforms consist of an F-box and seven WD repeats. Human beta TRCP2A shows 86% total amino acid identity with human beta TRCP. beta TRCP2 mRNA of 4.5 kb in size was detected almost ubiquitously. Sequence analyses on beta TRCP2 genomic clones revealed that the beta TRCP2 gene consists of at least 14 exons, Exons 1 and 4-14 are shared among all beta TRCP2 isoforms. beta TRCP2A of 508 amino acids lacks exons 2 and 3, beta TRCP2B of 529 amino acids contains exon 3, and beta TRCP2C of 542 amino acids contains exon 2. These results indicate that three beta TRCP2 isoforms are transcribed due to alternative splicing. The beta TRCP2 gene has been mapped to human chromosome 5q35.1 by fluorescence in situ hybridization.