The Golgi-associated γ-adaptin-related ADP-ribosylation factor-binding proteins (GGAs) are critical components of the transport machinery that mediates the trafficking of the mannose 6-phosphate receptors and associated cargo from the trans-Golgi network to the endosomes. The GGAs colocalize in vivo with the clathrin adaptor protein AP-1 and bind to AP-1 in vitro, suggesting that the two proteins may cooperate in packaging the mannose 6-phosphate receptors into clathrin-coated vesicles at the trans-Golgi network. Here, we demonstrate that the sequence, 382WNSF385, in the hinge region of GGA1 mediates its interaction with the AP-1 γ-ear. The Trp and Phe constitute critical amino acids in this interaction. The binding of Rabaptin5 to the AP-1 γ-ear, which occurs through a FXXΦ motif, is inhibited by a peptide encoding the GGA1 382WNSF 385 sequence. Moreover, mutations in the AP-1 γ-ear that abolish its interaction with Rabaptin5 also preclude its association with GGA1. These results suggest that the GGA1 WXXF-type and Rabaptin5 FXXΦ-type motifs bind to the same or highly overlapping sites in the AP-1 γ-ear. This binding is modulated by residues adjacent to the core motifs.