Adaptins are major structural components of heterotetrameric protein complexes called adaptors, which are involved in intracellular receptor transport via clathrin-coated vesicles. In mice, one of these adaptins has been shown to be encoded by two genes, alpha(A)-adaptin and alpha(C)-adaptin, the former of which is expressed as two alternatively spliced transcripts. Using positional cloning gene approaches, we were able to identify the human alpha(A)-adaptin gene, which consists of 24 exons spanning over 40 kb on chromosome 19q13.3 between the loci of the R-ras gene and the polynucleotide kinase phosphatase gene. The novel gene encodes a 977 amino acid, 107.6 kDa protein with 98% amino acid sequence identity to its murine ortholog. Human alpha(A)-adaptin is expressed as a full-length transcript in forebrain, skeletal muscle, spinal cord, cerebellum, salivary gland, heart and colon. It is also ubiquitously expressed in tissues and in ZR-75-1 breast cancer cells and LNCaP prostate carcinoma cells as a smaller variant generated by splicing out of an exon encoding 22 amino acids in the hinge region of the protein.