Sequestosome-1 gene is mapped on chromosome 5q35 containing 100 amino acids that mediates protein-protein interactions by binding to phosphotyrosine which provides instructions for making p62, a protein essential for bone remodeling in which old bone is broken down and new bone is created to replace it via chemical signaling pathways that promotes the formation of osteoclasts. It also involved in recycling worn-out cell parts and superfluous proteins, body’s immune responses, self-destruction of cells andinflammatory reactions.
Sequestosome-1 play a role in titin downstream signaling in muscle cells as well as regulates signaling cascade through ubiquitination. It also mediates the interaction between TRAF6 and CYLD implicated in cell differentiation, immune response, apoptosis and regulation of potassium channels. It regulates the activation of nuclear factor kappa-B signaling pathway together with TNF receptor-associated factor 6 as an adaptor protein in response to upstream signals.
Sequestosome-1 gene mutation is associated in Paget disease of bone, a metabolic bone disease affecting axial skeleton and typified by crucial areas of increased bone turn-over due to activated osteoclasts causing bone pain, pathological fractures, deformity, deafness, neurological complications and increased risk of osteosarcoma.
Gene name: SQSTM1
Protein name: Sequestosome-1