SQSTM1
SQSTM1 (sequestosome 1, also known as p62, p60, p62B, A170, PDB3 and OSIL) is a multifunctional ubiquitin-binding adaptor protein. It bridges polyubiquitinated cargo and autophagosomes in selective autophagy and acts as a scaffold in NF-kB signalling. Browse Assay Genie's current range of SQSTM1 research reagents below, or read on for the biology behind the target.
SQSTM1 is a molecular adapter required for selective macroautophagy, specifically aggrephagy, where it links polyubiquitinated proteins to autophagosomes. It first binds ubiquitinated proteins through its UBA domain and undergoes liquid-liquid phase separation, forming insoluble cytoplasmic inclusions known as p62 bodies. It then engages ATG8 family proteins on autophagosomes through its LIR motif, which recruits p62 bodies for autophagic clearance. SQSTM1 is itself degraded together with its ubiquitinated cargo, so its levels are often read as a reflection of autophagic flux.
Beyond aggrephagy, the SQSTM1 protein recruits ubiquitinated proteins to PML bodies in the nucleus and contributes to pexophagy in response to reactive oxygen species, bridging ubiquitinated PEX5 and autophagosomes. It activates the NFE2L2/NRF2 pathway by interacting with KEAP1, sequestering the BCR(KEAP1) complex in inclusion bodies so that NFE2L2/NRF2 accumulates in the nucleus and cytoprotective genes are expressed. It also promotes relocalisation of Lys-63-linked ubiquitinated STING1 to autophagosomes, helps organise the endosomal pathway by retaining vesicles in the perinuclear cloud after ubiquitination by RNF26, and sequesters TNS2 to promote its degradation.
In signalling, SQSTM1 acts as a scaffold with TRAF6 and mediates the interaction between TRAF6 and CYLD. It may regulate NF-kB activation by TNF, nerve growth factor and interleukin-1, and may take part in titin/TTN signalling in muscle cells. The SQSTM1 gene belongs to the ZZ-type zinc finger group, and alternatively spliced transcript variants have been described. Mutations in the gene cause sporadic and familial Paget disease of bone, which accounts for the earlier name PDB3.
SQSTM1 links ubiquitinated cargo to ATG8 family proteins on autophagosomes and is degraded with its cargo, making it central to studies of selective autophagy.
Through KEAP1 binding, SQSTM1 promotes nuclear accumulation of NFE2L2/NRF2 and expression of cytoprotective genes, linking autophagy to the redox response.
As a TRAF6 and CYLD scaffold, SQSTM1 contributes to NF-kB activation by upstream signals such as TNF and interleukin-1.
Mutations in the SQSTM1 gene cause sporadic and familial Paget disease of bone, making it a focus of bone biology research.
SQSTM1 is an adaptor that binds polyubiquitinated proteins through its UBA domain, forms p62 bodies and delivers them to autophagosomes via its LIR motif for degradation. It also activates NRF2 signalling through KEAP1 and acts as a TRAF6 scaffold in NF-kB signalling.
p62 is the best-known alias of SQSTM1, which is also listed as p60, p62B, A170, PDB3 and OSIL. The previous names are Paget disease of bone 3 and oxidative stress induced like. The official name, sequestosome 1, is used for the gene and the protein, Sequestosome-1.
Mouse and rat both have a Sqstm1 ortholog. In humans, mutations in SQSTM1 result in sporadic and familial Paget disease of bone. Check the datasheet of any product for its validated reactivity.
Autophagy adaptors, ubiquitin-pathway proteins and NF-kB and NRF2 signalling partners with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q13501; product specifications from Assay Genie datasheets.