SQSTM1 : sequestosome 1

Description

The SQSTM1 (sequestosome 1) is a protein-coding gene located on chromosome 5.

The SQSTM1 gene provides instructions for making a protein called p62. This protein plays an important role in bone remodeling, a normal process in which old bone is broken down and new bone is created to replace it. The p62 protein helps regulate this process through its role in a chemical signaling pathway that promotes the formation of osteoclasts. Osteoclasts are specialized cells that break down bone tissue during bone remodeling.Studies suggest that p62 may have other functions in addition to its role in bone remodeling. It may be involved in recycling worn-out cell parts and unneeded proteins (autophagy), the self-destruction of cells (apoptosis), and the body's immune responses and inflammatory reactions.

SQSTM1 is a molecular adapter that plays a critical role in selective macroautophagy (aggrephagy), a process that removes damaged or unwanted cellular components. It acts as a bridge between polyubiquitinated proteins, which are tagged for degradation, and autophagosomes, the cellular machinery responsible for engulfing and breaking down these tagged proteins. This process is essential for maintaining cellular health and function. SQSTM1 achieves this by first mediating the assembly and removal of ubiquitinated proteins through liquid-liquid phase separation, a process that involves the formation of insoluble cytoplasmic inclusions known as p62 bodies. These bodies are then recruited to autophagosomes via SQSTM1's interaction with ATG8 family proteins. Finally, both SQSTM1 and the ubiquitinated proteins are degraded within the autophagosomes. In addition to its role in aggrephagy, SQSTM1 also participates in other critical cellular processes, including autophagy of peroxisomes (pexophagy) in response to reactive oxygen species (ROS), activation of the NFE2L2/NRF2 pathway, relocalization of ubiquitinated STING1, endosome organization, and regulation of NFKB1 activation. It interacts with a wide array of proteins, including those involved in ubiquitination, autophagy, signaling pathways, and cytoskeletal organization. Its interactions with various proteins contribute to its diverse roles in maintaining cellular homeostasis and response to stress.

SQSTM1 is also known as A170, DMRV, EBIAP, FTDALS3, NADGP, OSIL, PDB3, ZIP3, p60, p62, p62B.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing