Recombinant Human SQSTM1 / p62 protein

Specifications

Form

Liquid

Additional notes

ab95320 is purified using conventional chromatography techniques

General info

Function

The protein expressed by the SQSTM1 gene is an autophagy receptor essential for selective macroautophagy (aggrephagy). It acts as a bridge between polyubiquitinated cargo and autophagosomes, interacting with both the cargo and an autophagy modifier from the MAP1 LC3 family. Alongside WDFY3, it plays a role in forming and autophagically degrading cytoplasmic ubiquitin-containing inclusions and recruiting ubiquitinated proteins to nuclear PML bodies. SQSTM1 may regulate NFKB1 activation by TNF-alpha, nerve growth factor (NGF), and interleukin-1, and may influence titin/TTN signaling in muscle cells. It may also affect signaling cascades via ubiquitination and be involved in cell differentiation, apoptosis, immune response, and regulation of potassium channels. The protein is involved in endosome organization by retaining vesicles in the perinuclear cloud; ubiquitination by RNF26 allows it to attract vesicle-associated adapters, forming a molecular bridge to organize endosomal pathways. Additionally, it promotes the relocalization of Lys-63-linked ubiquitinated STING1 to autophagosomes and acts as an activator of the NFE2L2/NRF2 pathway by interacting with KEAP1, which inactivates the BCR(KEAP1) complex, resulting in nuclear accumulation of NFE2L2/NRF2 and expression of cytoprotective genes. This supplementary information is collated from multiple sources and compiled automatically.

Post-translational modifications

Phosphorylation at Ser-407 by ULK1 destabilizes the UBA dimer interface and increases binding affinity to ubiquitinated proteins (By similarity). Phosphorylation at Ser-407 also primes for subsequent phosphorylation at Ser-403 (By similarity). Phosphorylation at Ser-403 by CK2 or ULK1 promotes binding to ubiquitinated proteins by increasing the affinity between the UBA domain and polyubiquitin chains (PubMed:22017874, PubMed:25040165). Phosphorylation at Ser-403 by ULK1 is stimulated by SESN2 (PubMed:25040165). Phosphorylated at Ser-403 by TBK1, leading to promote relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (PubMed:29496741). Phosphorylation at Ser-349 by ULK1 promotes interaction with KEAP1 and inactivation of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes (PubMed:37306101). Phosphorylated in vitro by TTN (PubMed:15802564).. Ubiquitinated by UBE2J1 and RNF26 at Lys-435: ubiquitinated SQSTM1 attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport (PubMed:27368102, PubMed:33472082). Ubiquitination by UBE2D2 and UBE2D3 increases its ability to bind polyubiquitin chains by destabilizing the UBA dimer interface (PubMed:28322253). Deubiquitination by USP15 releases target vesicles for fast transport into the cell periphery (PubMed:27368102). Ubiquitinated by the BCR(KEAP1) complex at Lys-420, increasing SQSTM1 sequestering activity and promoting its degradation (PubMed:28380357). Ubiquitinated via 'Lys-29' and 'Lys-33'-linked polyubiquitination leading to xenophagic targeting of bacteria and inhibition of their replication (PubMed:27880896).. Acetylated at Lys-420 and Lys-435 by KAT5/TIP60, promotes activity by destabilizing the UBA dimer interface and increases binding affinity to ubiquitinated proteins (PubMed:31857589). Deacetylated by HDAC6 (PubMed:31857589).. Palmitoylation at Cys-289 and Cys-290 by ZDHHC19 is required for efficient autophagic degradation of SQSTM1-cargo complexes by promoting affinity for ATG8 proteins and recruitment of p62 bodies to autophagosomes (PubMed:37802024). Dealmitoylated at Cys-289 and Cys-290 by LYPLA1 (PubMed:37802024).. (Microbial infection) Cleaved by S.pyogenes SpeB protease; leading to its degradation (PubMed:24331465). Degradation by SpeB prevents autophagy, promoting to S.pyogenes intracellular replication (PubMed:24331465).. (Microbial infection) Deubiquitinated by Epstein-Barr virus BPLF1; leading to inhibition of the recruitment of MAP1LC3A/LC3 to SQSTM1-positive structures.

Subcellular localisation

Late endosome