Sqstm1
entrez
113894
canonical
uniprot
O08623
canonical
ensembl
ENSRNOG00000003147
resolver
ensembl
ENSRNOG00055019045
resolver
ensembl
ENSRNOG00060019383
resolver
ensembl
ENSRNOG00065006177
resolver
ensp
ENSRNOP00000004308
resolver
ensp
ENSRNOP00000056021
resolver
genesymbol
Sqstm1
resolver
genesymbol_syn
Zip
resolver
uniprot
Q8CH59
resolver
uniprot_entry
SQSTM_RAT
resolver
uniprot_sec
Q8CH59
resolver
amino_acid_sequence
MASLTVKAYLLGKEEAAREIRRFSFCFSPEPEAEAAAGPGPCERLLSRVAVLFPALRPGGFQAHYRDEDGDLVAFSSDEELTMAMSYVKDDIFRIYIKEKKECRREHRPPCAQEARSMVHPNVICDGCNGPVVGTRYKCSVCPDYDLCSVCEGKGLHREHSKLIFPNPFGHLSDSFSHSRWLRKLKHGHFGWPGWEMGPPGNWSPRPPRAGDGRPCPTAESASAPSEDPNVNFLKNVGESVAAALSPLGIEVDIDVEHGGKRSRLTPTSAESSSTGTEDKSGTQPSSCSSEVSKPDGAGEGPAQSLTEQMKKIALESVGQPEELMESDNCSGGDDDWTHLSSKEVDPSTGELQSLQMPESEGPSSLDPSQEGPTGLKEAALYPHLPPEADPRLIESLSQMLSMGFSDEGGWLTRLLQTKNYDIGAALDTIQYSKHPPPL
uniprot
proteins
function
FUNCTION: Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes (By similarity). Promotes the recruitment of ubiquitinated cargo proteins to autophagosomes via multiple domains that bridge proteins and organelles in different steps (By similarity). SQSTM1 first mediates the assembly and removal of ubiquitinated proteins by undergoing liquid-liquid phase separation upon binding to ubiquitinated proteins via its UBA domain, leading to the formation of insoluble cytoplasmic inclusions, known as p62 bodies (By similarity). SQSTM1 then interacts with ATG8 family proteins on autophagosomes via its LIR motif, leading to p62 body recruitment to autophagosomes, followed by autophagic clearance of ubiquitinated proteins (By similarity). SQSTM1 is itself degraded along with its ubiquitinated cargos (By similarity). Also required to recruit ubiquitinated proteins to PML bodies in the nucleus (By similarity). Also involved in autophagy of peroxisomes (pexophagy) in response to reactive oxygen species (ROS) by acting as a bridge between ubiquitinated PEX5 receptor and autophagosomes (By similarity). Acts as an activator of the NFE2L2/NRF2 pathway via interaction with KEAP1: interaction inactivates the BCR(KEAP1) complex by sequestering the complex in inclusion bodies, promoting nuclear accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective genes (By similarity). Promotes relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (By similarity). Involved in endosome organization by retaining vesicles in the perinuclear cloud: following ubiquitination by RNF26, 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 (By similarity). Sequesters tensin TNS2 into cytoplasmic puncta, promoting TNS2 ubiquitination and proteasomal degradation (By similarity). May regulate the activation of NFKB1 by TNF, nerve growth factor (NGF) and interleukin-1 (PubMed:11244088, PubMed:11500922). May play a role in titin/TTN downstream signaling in muscle cells (By similarity). Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). {ECO:0000250|UniProtKB:Q13501, ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:11500922}.; FUNCTION: [Isoform 1]: More potent than isoform 2 to stimulate PRKCZ-dependent phosphorylation of KCNAB2. {ECO:0000269|PubMed:10477520}.
uniprot
proteins
mass_dalton
47681
uniprot
proteins
mutagenesis
MUTAGEN 7; /note="K->A: Loss of interaction with PRKCI."; /evidence="ECO:0000269|PubMed:15143057"; MUTAGEN 21..22; /note="RR->AA: Reduces interaction with PRKCI."; /evidence="ECO:0000269|PubMed:15143057"; MUTAGEN 67; /note="D->A: No effect on interaction with PRKCI. Abolishes homooligomerization; when associated with A-67."; /evidence="ECO:0000269|PubMed:15143057, ECO:0000269|PubMed:19728111"; MUTAGEN 69; /note="D->A: Abolishes homooligomerization; when associated with A-67."; /evidence="ECO:0000269|PubMed:19728111"; MUTAGEN 94; /note="R->A: Reduces interaction with PRKCI."; /evidence="ECO:0000269|PubMed:15143057
uniprot
proteins
post_translational_modification
PTM: Phosphorylated (PubMed:9177193). Phosphorylation at Ser-406 by ULK1 destabilizes the UBA dimer interface and increases binding affinity to ubiquitinated proteins. Phosphorylation at Ser-406 also primes for subsequent phosphorylation at Ser-402 (By similarity). Phosphorylation at Ser-402 by CK2 or ULK1 promotes binding to ubiquitinated proteins by increasing the affinity between the UBA domain and polyubiquitin chains. Phosphorylation at Ser-402 by ULK1 is stimulated by SESN2. Phosphorylated at Ser-402 by TBK1, leading to promote relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes. Phosphorylation at Ser-348 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. Phosphorylated in vitro by TTN (By similarity). {ECO:0000250|UniProtKB:Q13501, ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:9177193}.; PTM: Ubiquitinated by UBE2J1 and RNF26 at Lys-434: 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. Ubiquitination by UBE2D2 and UBE2D3 increases its ability to bind polyubiquitin chains by destabilizing the UBA dimer interface. Deubiquitination by USP15 releases target vesicles for fast transport into the cell periphery. Ubiquitinated by the BCR(KEAP1) complex at Lys-419, increasing SQSTM1 sequestering activity and promoting its degradation. Ubiquitinated via 'Lys-29' and 'Lys-33'-linked polyubiquitination leading to xenophagic targeting of bacteria and inhibition of their replication. {ECO:0000250|UniProtKB:Q13501}.; PTM: Acetylated at Lys-419 and Lys-434 by KAT5/TIP60, promotes activity by destabilizing the UBA dimer interface and increases binding affinity to ubiquitinated proteins. Deacetylated by HDAC6. {ECO:0000250|UniProtKB:Q13501}.; PTM: Palmitoylation at Cys-288 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. Dealmitoylated at Cys-288 by LYPLA1. {ECO:0000250|UniProtKB:Q13501}.
uniprot
proteins
pubmed
10366737
uniprot
proteins
pubmed
10477520
uniprot
proteins
pubmed
11162503
uniprot
proteins
pubmed
11244088
uniprot
proteins
pubmed
11500922
uniprot
proteins
pubmed
11981755
uniprot
proteins
pubmed
12431995
uniprot
proteins
pubmed
15143057
uniprot
proteins
pubmed
15158159
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15802564
uniprot
proteins
pubmed
16079148
uniprot
proteins
pubmed
19728111
uniprot
proteins
pubmed
22673903
uniprot
proteins
pubmed
9177193
uniprot
proteins
sequence_length
439
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasmic vesicle, autophagosome {ECO:0000250|UniProtKB:Q13501}. Preautophagosomal structure {ECO:0000250|UniProtKB:Q13501}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q64337}. Nucleus, PML body {ECO:0000250|UniProtKB:Q13501}. Late endosome {ECO:0000250|UniProtKB:Q13501}. Lysosome {ECO:0000250|UniProtKB:Q13501}. Nucleus {ECO:0000250|UniProtKB:Q64337}. Endoplasmic reticulum {ECO:0000250|UniProtKB:Q13501}. Cytoplasm, myofibril, sarcomere {ECO:0000269|PubMed:15802564}. Note=In cardiac muscle, localizes to the sarcomeric band (PubMed:15802564). Localizes to cytoplasmic membraneless inclusion bodies, known as p62 bodies, containing polyubiquitinated protein aggregates (By similarity). In protein aggregate diseases of the liver, found in large amounts in Mallory bodies of alcoholic and nonalcoholic steatohepatitis, hyaline bodies in hepatocellular carcinoma, and in SERPINA1 aggregates. Enriched in Rosenthal fibers of pilocytic astrocytoma. In the cytoplasm, observed in both membrane-free ubiquitin-containing protein aggregates (sequestosomes) and membrane-surrounded autophagosomes. Colocalizes with TRIM13 in the perinuclear endoplasmic reticulum. Co-localizes with TRIM5 in cytoplasmic bodies. When nuclear export is blocked by treatment with leptomycin B, accumulates in PML bodies (By similarity). {ECO:0000250|UniProtKB:Q13501, ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:15802564}.
uniprot
proteins