We have identified two closely related human proteins (sigma(3A) and s
igma(3B)) that are homologous to the small chains, sigma(1) and sigma(
2), of clathrin-associated adaptor complexes, Northern and Western blo
t analyses demonstrate that the products of both the sigma(3A) and sig
ma(3B) genes are expressed in a wide variety of tissues and cell lines
. sigma(3A) and sigma(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 co
rresponds to the medium chain homolog p47A, and the 140 kDa protein is
a homolog of the neuron-specific protein beta-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. Immunofluoresc
ence microscopy analyses show that the sigma(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 sigma(3) chains are components of a novel, ubiquitous adaptor-lik
e complex involved in the recognition of tyrosine-based sorting signal
s.