C-terminal domain of TBC1 domain family member 23, and similar proteins
This family contains the C-terminal domain of Tre2-Bub2-Cdc16 (TBC) family 23 (TBC1D23), which adopts a Pleckstrin homology (PH) domain fold. It selectively binds to phosphoinositides, in particular, PtdIns(4)P, through one surface while it binds FAM21 via the opposite surface. TBC1D23, which is highly conserved in many eukaryotes but missing in plants and fungi, also possesses an N-terminal domain which is a catalytically inactive TBC domain. TBC1D23 encodes a protein functioning in endosome-to-Golgi trafficking in cells; it is a specificity determinant that links the vesicle to the target membrane. Homozygous mutations of TBC1D23 have been found in patients diagnosed with pontocerebellar hypoplasia (PCH), a group of neurological disorders that affect the brain development, particularly, the pons and cerebellum. Mutation of key residues of TBC1D23 (or FAM21) selectively disrupts the endosomal vesicular trafficking toward the Trans-Golgi Network. This C-terminal domain is missing in some PCH patients.
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