Abstract

We have identified two closely related human proteins (_3A and _3B) that are homologous to the small chains, ₁ and ₂, of clathrin-associated adaptor complexes. Northern and Western blot analyses demonstrate that the products of both the _3A and _3B genes are expressed in a wide variety of tissues and cell lines. _3A and _3B are components of a large complex, named AP-3, that also contains proteins of apparent molecular masses of 47, 140 and 160 kDa. In non-neuronal cells, the 47 kDa protein most likely corresponds to the medium chain homolog p47A, and the 140 kDa protein is a homolog of the neuron-specific protein -NAP. Like other members of the medium-chain family, the p47A chain is capable of interacting with the tyrosine-based sorting signal YQRL from TGN38. Immunofluorescence microscopy analyses show that the ₃-containing complex is present both in the area of the TGN and in peripheral structures, some of which contain the transferrin receptor. These results suggest that the ₃ chains are components of a novel, ubiquitous adaptor-like complex involved in the recognition of tyrosine-based sorting signals.