Yokoyama-Kobayashi et al. (1995) developed a system to detect N-terminal secretory signal sequences, called the fibrin sheet method, based on the detection of secreted protein fused to a urokinase plasminogen activator protein having fibrinolytic activity.

Yokoyama-Kobayashi et al. (1999) adopted this system to identify cDNAs encoding type II signal anchors, in which the N-terminal signal sequence is uncleaved and remains in the membrane, facing the cytoplasm. They isolated a cDNA encoding TMEM5, which they termed HP10481, from a phorbol ester-stimulated U937 monocyte cDNA library. TMEM5 is predicted to encode a 443-amino acid type II transmembrane protein.