SQSTM1/p62 Antibody (YA6343)

Cytoplasmic vesicle, autophagosome; Preautophagosomal structure; Cytoplasm, cytosol; Nucleus, PML body; Late endosome; Lysosome; Nucleus; Endoplasmic reticulum; Cytoplasm, myofibril, sarcomere

Tissue_specificity:Ubiquitously expressed.

Induction:By proteasomal inhibitor PSI and prostaglandin J2 (PGJ2) (at protein level) . By phorbol 12-myristate 13-acetate (PMA) . Expression is directly activated by NFE2L2/NRF2; creating a positive feedback loop (PubMed:20452972)

Q13501 has 2 isomers: Q13501-1: 47687 Da (predicted); Q13501-2: 38629 Da (predicted).
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

Homooligomer or heterooligomer; may form homotypic arrays (PubMed:12887891, PubMed:19931284). Dimerization interferes with ubiquitin binding (PubMed:19931284). Component of a ternary complex with PAWR and PRKCZ (PubMed:11755531). Forms a complex with JUB/Ajuba, PRKCZ and TRAF6 (PubMed:15870274). Identified in a complex with TRAF6 and CYLD (By similarity). Identified in a heterotrimeric complex with ubiquitin and ZFAND5, where ZFAND5 and SQSTM1 both interact with the same ubiquitin molecule (PubMed:21923101). Interacts (via LIR motif) with MAP1LC3A and MAP1LC3B, as well as with other ATG8 family members, including GABARAP, GABARAPL1 and GABARAPL2; these interactions are necessary for the recruitment MAP1 LC3 family members to inclusion bodies containing polyubiquitinated protein aggregates and for their degradation by autophagy (PubMed:16286508, PubMed:17580304, PubMed:22421968, PubMed:24089205, PubMed:24668264). Interacts directly with PRKCI and PRKCZ (PubMed:10356400, PubMed:12813044, PubMed:12887891, PubMed:9566925). Interacts with EBI3, LCK, RASA1, NR2F2, NTRK1, NTRK2, NTRK3, NBR1, MAP2K5 and MAPKAPK5 (PubMed:10708586, PubMed:11244088, PubMed:12471037, PubMed:8551575, PubMed:8618896, PubMed:8650207, PubMed:8910285). Upon TNF-alpha stimulation, interacts with RIPK1 probably bridging IKBKB to the TNF-R1 complex composed of TNF-R1/TNFRSF1A, TRADD and RIPK1 (PubMed:10747026). Interacts with the proteasome subunits PSMD4 and PSMC2 (PubMed:15340068). Interacts with TRAF6 (PubMed:10747026). Interacts with 'Lys-63'-linked polyubiquitinated MAPT/TAU (PubMed:15953362). Interacts with FHOD3 (PubMed:21149568). Interacts with CYLD (PubMed:32185393). Interacts with SESN1 (PubMed:23274085). Interacts with SESN2 (PubMed:23274085, PubMed:25040165). Interacts with ULK1 (PubMed:25040165). Interacts with UBD (PubMed:25422469). Interacts with WDR81; the interaction is direct and regulates the interaction of SQSTM1 with ubiquitinated proteins (PubMed:28404643). Interacts with WDFY3; this interaction is required to recruit WDFY3 to cytoplasmic bodies and to PML bodies (PubMed:20168092). Interacts with LRRC25 (PubMed:29288164). Interacts with STING1; leading to relocalization of STING1 to autophagosomes (PubMed:29496741). Interacts (when phosphorylated at Ser-349) with KEAP1; the interaction is direct and inactivates the BCR(KEAP1) complex by sequestering KEAP1 in inclusion bodies, promoting its degradation (PubMed:20452972, PubMed:20495340, PubMed:37306101). Interacts with MOAP1; promoting dissociation of SQSTM1 inclusion bodies that sequester KEAP1 (PubMed:33393215). Interacts with GBP1 (By similarity). Interacts with TAX1BP1 (PubMed:34471133). Interacts with (ubiquitinated) PEX5; specifically binds PEX5 ubiquitinated at 'Lys-209' in response to reactive oxygen species (ROS) (PubMed:26344566). Interacts (via PB1 domain) with TNS2; the interaction leads to sequestration of TNS2 in cytoplasmic aggregates with SQSTM1 and promotes TNS2 ubiquitination and proteasomal degradation (PubMed:25101860). Interacts with IRS1; the interaction is disrupted by the presence of tensin TNS2 (PubMed:25101860). Interacts with TRIM5 (PubMed:20357094, PubMed:25127057). Interacts with TRIM11 (when ubiquitinated); promoting AIM2 recruitment to autophagosomes and autophagy-dependent degradation of AIM2 (PubMed:27498865). Interacts with TRIM13 (PubMed:22178386). Interacts with TRIM16 (PubMed:30143514). Interacts with TRIM23 (PubMed:28871090). Interacts with TRIM50 (PubMed:22792322). Interacts with TRIM55 (PubMed:15802564). Interacts with ECSIT; this interaction inhibits TLR4 signaling via functional regulation of the TRAF6-ECSIT complex (PubMed:31281713). Interacts with GABRR1, GABRR2 and GABRR3 (By similarity). Interacts with WDR83 (PubMed:38103557). Interacts with GRB2 (PubMed:35831301). Interacts with USP12; the interaction is independent of USP12 deubiquitinase activity and may be involved in regulation of autophagic flux (PubMed:30266909). Interacts with ASB6 (PubMed:34164402)

Q13501