PLEKHM1
Description
The PLEKHM1 (pleckstrin homology and RUN domain containing M1) is a protein-coding gene located on chromosome 17.
Pleckstrin homology domain-containing family M member 1, also known as PLEKHM1 or the 162 kDa adapter protein, is a protein encoded by the PLEKHM1 gene in humans. It plays a crucial role in vesicular transport within osteoclasts. PLEKHM1 contains a C-terminal Rubicon Homology (RH) domain, which interacts with the small GTPase Rab7. This domain is shared with other family members, Rubicon and Pacer, which are involved in regulating autophagy. Mutations in the PLEKHM1 gene are associated with osteopetrosis, specifically OPTB6.
PLEKHM1 acts as a multivalent adapter protein that regulates Rab7-dependent and HOPS complex-dependent fusion events in the endolysosomal system, connecting autophagic and endocytic trafficking pathways. It binds to both RAB7A and ARL8B simultaneously, promoting clustering and fusion of late endosomes and lysosomes. PLEKHM1 is essential for late endolysosomal maturation, facilitating the degradation of growth factor receptors via endocytosis and clearing autophagosomes. Its interaction with Arl8b is crucial for the final maturation of autophagosomes and for mediating autophagosome-lysosome fusion. It positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts. PLEKHM1 may negatively regulate endocytic transport from early to late endosomes/lysosomes due to its association with Rab7. It might play a role in sialyl-lex-mediated apoptotic signal transduction. PLEKHM1 is involved in bone resorption.
PLEKHM1 is also known as AP162, B2, OPTA3, OPTB6.
