| Primary Identifier | IPR042827 | Type | Domain |
| Short Name | PLEKHM1_PH |
| description | PLEKHM1 is a ubiquitously expressed protein involved in the regulation of osteoclast function and bone resorption []. It may function as an adaptor protein that acts as a central hub to integrate endocytic and autophagic pathways at the lysosome []. PLEKHM1 contains an N-terminal RUN domain (RPIP8/RaP2 interacting protein 8, UNC-14 and NESCA/new molecule containing SH3 at the carboxyl-terminus), followed by a PH domain, and either a C1 domain or a DUF4206 domain at its C terminus. The RUN domain is thought to be involved in Rab-mediated membrane trafficking, possibly as a Rab-binding site. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner []. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity []. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane []. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes []. |
