GPR34 topogenesis and cell surface trafficking are regulated by positive-inside rule.
A tri-basic motif in the first intracellular loop is the key topogenic signal.
Disruption of the motif led to erroneous topology and trafficking arrest in Golgi.
Exogenous N-terminal signal sequence rectified the topology and trafficking.
Biochemical properties of the key native conformational epitope were elucidated.