SLC15A4 (PHT1) interaction proteomics

Human genetics and mouse models provide compelling evidence for the involvement of SLC15A4 in endosomal TLR activation. To gain an understanding of the molecular mechanism, we set out to identify its binding partners by interaction proteomics. TAP-MS/MS analysis of different SLC15A4 protein variants provided a global view of the SLC15A4 interaction landscape. Among the proteins detected, the uncharacterized protein CXorf21 emerged as a prominent and specific binder. CXorf21 is a X chromosome-encoded gene which has also been linked to SLE by a GWAS. CXorf21 was robustly identified with all the SLC15A4 constructs tested, indicating that the interaction does not require the N-terminal or central cytoplasmic region of the transporter. Reciprocal TAP-MS/MS analysis using tagged CXorf21 identified endogenous SLC15A4 as a specific interactor.