AMSH/STAMBP: ProductsAssociated Molecule with the SH3 Domain of STAM (AMSH), also known as STAM Binding Protein (STAMBP), is a 424 amino acid (aa) zinc metalloprotease member of the peptidase M67C class of enzymes with a predicted molecular weight of 50 kDa. The mouse and rat AMSH/STAMBP orthologs share 83% and 84% aa sequence identity with the human protein, respectively. AMSH/STAMBP is ubiquitously expressed and functions at endosomes where it opposes Ubiquitin-dependent sorting and recycling of receptors to lysosomes. The ability of AMSH/STAMBP to cleave K63-linked, but not K48-linked, poly-Ubiquitin chains is mediated by a JAMM motif (aa 335-348). Receptor substrates for AMSH/STAMBP include EGF R and Erb2. AMSH/STAMBP also functions in cytokine signaling and participates in cMyc induction by IL-2 or GM-CSF, as well as bone morphogenic protein (BMP) signaling via inhibition of Smad proteins. AMSH/STAMBP knockout mice show early-onset neurodegeneration and increased protein deposits in the brain, suggesting that AMSH/STAMBP may contribute to neurodegenerative diseases such as Alzheimerâs Disease, ALS, or Parkinsonâs Disease.