MEPE (matrix extracellular phosphoglycoprotein; also OF45) is a 56-58kD member of the SIBLING protein family. It is expressed by osteocytes, osteoblasts, odontoblasts and chondrocytes. MEPE is found both intra- and extracellularly. Within the cell, it binds to CHK1. This protects CHK1 from degradation, and the cell from DNA damage. Extracellularly, it binds to Phex, which protects it from cathepsin B proteolysis. Undegraded, it promotes bone vascularization and blocks bone resorption. Following cleavage after Arg410 (in mouse), a 2kD ASARM fragment is generated that, when phosphorylated, blocks mineralization. Mature mouse MEPE is 417aa in length. It contains an RGD motif and ASARM domain (aa416-433). In addition to its 57kD form, 70kD, 42-45kD and 30-35kD forms of mouse MEPE have been reported. Whether they are cleavage forms or products of glycosylation is unclear. Over aa147-433, mouse MEPE shares 77% and 57% aa identity with rat and human MEPE, respectively.
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