3.A.1.209.2
Homodimeric transporter ABCB9 or TAPL of 766 aas and 10 TMSs in a 4 + 2 + 2 + 2 TMS arrangement. It transports a broad spectrum of peptides (low affinity) from the cytosol to the lysosomal lumen and displays a broad peptide length specificity from 6-mer up to at least 59-mer peptides with an optimum of 23-mers. It favors positively charged, aromatic and hydrophobic residues in the N- and C-terminal positions whereas negatively charged residues as well as asparagine and methionine are not favored. TapL transports a broad range of peptides of 6-60aas (23aas optimal). It has also been detected in the ER. It is stabilized by interaction with LAMP-1 and LAMP-2 (see 9.A.16) (Demirel et al., 2012).  The protein consists of a core transporter plus an N-terminal transmembrane domain (TMD0) required to tageting to the lysosome and for interactions with LAMP-1 and -2 (Tumulka et al. 2013). TMD0 has a four transmembrane helix topology with a short helical segment in a lysosomal loop (Bock et al. 2018). Lysosomal targeting is determined by membrane localized charged residues (Graab et al. 2019).  D278 seems to be involved in bidirectional interdomain communication mediated by a network of polar interactions, whereas the two residues in the cytosolic extension of transmembrane helix 3 are involved in regulation of ATP hydrolysis, most likely by stabilization of the outward-facing conformation (Lindt et al. 2024). .