Sqstm1
entrez
18412
canonical
uniprot
Q64337
canonical
ensembl
ENSMUSG00000015837
resolver
ensp
ENSMUSP00000015981
resolver
ensp
ENSMUSP00000099835
resolver
ensp
ENSMUSP00000324972
resolver
genesymbol
Sqstm1
resolver
genesymbol_syn
A170
resolver
genesymbol_syn
STAP
resolver
uniprot
Q99JM8
resolver
uniprot_entry
SQSTM_MOUSE
resolver
uniprot_sec
Q99JM8
resolver
amino_acid_sequence
MASFTVKAYLLGKEEATREIRRFSFCFSPEPEAEAQAAAGPGPCERLLSRVAVLFPTLRPGGFQAHYRDEDGDLVAFSSDEELTMAMSYVKDDIFRIYIKEKKECRREHRPPCAQEAPRNMVHPNVICDGCNGPVVGTRYKCSVCPDYDLCSVCEGKGLHREHSKLIFPNPFGHLSDSFSHSRWLRKLKHGHFGWPGWEMGPPGNWSPRPPRAGDGRPCPTAESASAPPEDPNVNFLKNVGESVAAALSPLGIEVDIDVEHGGKRSRLTPTTPESSSTGTEDKSNTQPSSCSSEVSKPDGAGEGPAQSLTEQMKKIALESVGQPEEQMESGNCSGGDDDWTHLSSKEVDPSTGELQSLQMPESEGPSSLDPSQEGPTGLKEAALYPHLPPEADPRLIESLSQMLSMGFSDEGGWLTRLLQTKNYDIGAALDTIQYSKHPPPL
uniprot
proteins
function
FUNCTION: Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes (PubMed:25723488, PubMed:33397898, PubMed:37306101). Promotes the recruitment of ubiquitinated cargo proteins to autophagosomes via multiple domains that bridge proteins and organelles in different steps (PubMed:25723488, PubMed:33397898). 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 (PubMed:33397898). 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 (PubMed:33397898). 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 (PubMed:20173742, PubMed:20421418, PubMed:24011591, PubMed:33397898, PubMed:37306101). 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 (By similarity). May play a role in titin/TTN downstream signaling in muscle cells (By similarity). Adapter that mediates the interaction between TRAF6 and CYLD (PubMed:14960283, PubMed:18382763). {ECO:0000250|UniProtKB:Q13501, ECO:0000269|PubMed:14960283, ECO:0000269|PubMed:18382763, ECO:0000269|PubMed:20173742, ECO:0000269|PubMed:20421418, ECO:0000269|PubMed:24011591, ECO:0000269|PubMed:25723488, ECO:0000269|PubMed:33397898, ECO:0000269|PubMed:37306101}.
uniprot
proteins
mass_dalton
48163
uniprot
proteins
mutagenesis
MUTAGEN 7; /note="K->A: Abolished oligomerization without affecting interaction with KEAP1; when associated with A-69."; /evidence="ECO:0000269|PubMed:20173742, ECO:0000269|PubMed:33397898"; MUTAGEN 69; /note="D->A: Abolished oligomerization without affecting interaction with KEAP1; when associated with A-7."; /evidence="ECO:0000269|PubMed:20173742, ECO:0000269|PubMed:33397898"; MUTAGEN 337..339; /note="DDD->AAA: Greatly decreases interaction with MAP1LC3B."; /evidence="ECO:0000269|PubMed:18524774"; MUTAGEN 340..343; /note="WTHL->ATHA: Abolished interaction with ATG8 family proteins."; /evidence="ECO:0000269|PubMed:33397898"; MUTAGEN 340; /note="W->A: Greatly decreases interaction with MAP1LC3B."; /evidence="ECO:0000269|PubMed:18524774"; MUTAGEN 343; /note="L->A: Greatly decreases interaction with MAP1LC3B."; /evidence="ECO:0000269|PubMed:18524774"; MUTAGEN 349..354; /note="DPSTGE->AAAAAA: Abolishes interaction with KEAP1."; /evidence="ECO:0000269|PubMed:20421418"; MUTAGEN 349; /note="D->A: Strongly decreased interaction with KEAP1."; /evidence="ECO:0000269|PubMed:20173742"; MUTAGEN 350; /note="P->A: Strongly decreased interaction with KEAP1."; /evidence="ECO:0000269|PubMed:20173742"; MUTAGEN 351; /note="S->A: Does not affect interaction with KEAP1. Decreased phosphorylation by ULK1."; /evidence="ECO:0000269|PubMed:20173742, ECO:0000269|PubMed:24011591"; MUTAGEN 351; /note="S->E: Mimics phosphorylation; promotes interaction with KEAP1 and nuclear accumulation of NFE2L2/NRF2."; /evidence="ECO:0000269|PubMed:24011591, ECO:0000269|PubMed:37306101"; MUTAGEN 352; /note="T->A: Strongly decreased interaction with KEAP1."; /evidence="ECO:0000269|PubMed:20173742, ECO:0000269|PubMed:33397898"; MUTAGEN 353; /note="G->A: Strongly decreased interaction with KEAP1."; /evidence="ECO:0000269|PubMed:20173742"; MUTAGEN 354; /note="E->A: Strongly decreased interaction with KEAP1."; /evidence="ECO:0000269|PubMed:20173742"; MUTAGEN 409; /note="S->A: Decreased but not abolished phosphorylation by ULK1."; /evidence="ECO:0000269|PubMed:25723488"; MUTAGEN 409; /note="S->E: Mimics phosphorylation; increased affinity for ubiquitinated proteins, promoting autophagic degradation."; /evidence="ECO:0000269|PubMed:25723488
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-409 by ULK1 destabilizes the UBA dimer interface and increases binding affinity to ubiquitinated proteins (PubMed:25723488). Phosphorylation at Ser-409 also primes for subsequent phosphorylation at Ser-405 (PubMed:25723488). Phosphorylation at Ser-405 by CK2 or ULK1 promotes binding to ubiquitinated proteins by increasing the affinity between the UBA domain and polyubiquitin chains (By similarity). Phosphorylation at Ser-405 by ULK1 is stimulated by SESN2 (By similarity). Phosphorylated at Ser-405 by TBK1, leading to promote relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (By similarity). Phosphorylation at Ser-351 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:24011591, PubMed:37306101). Phosphorylated in vitro by TTN (By similarity). {ECO:0000250|UniProtKB:Q13501, ECO:0000269|PubMed:24011591, ECO:0000269|PubMed:25723488, ECO:0000269|PubMed:37306101}.; PTM: Ubiquitinated by UBE2J1 and RNF26 at Lys-437: 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-422, 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-422 and Lys-437 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-291 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-291 by LYPLA1. {ECO:0000250|UniProtKB:Q13501}.
uniprot
proteins
pubmed
10458914
uniprot
proteins
pubmed
11162503
uniprot
proteins
pubmed
12745069
uniprot
proteins
pubmed
14960283
uniprot
proteins
pubmed
15345747
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15890008
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16286508
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
18382763
uniprot
proteins
pubmed
18524774
uniprot
proteins
pubmed
19131326
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20173742
uniprot
proteins
pubmed
20421418
uniprot
proteins
pubmed
20495340
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21551061
uniprot
proteins
pubmed
22792322
uniprot
proteins
pubmed
24011591
uniprot
proteins
pubmed
25040165
uniprot
proteins
pubmed
25723488
uniprot
proteins
pubmed
33397898
uniprot
proteins
pubmed
37306101
uniprot
proteins
pubmed
8806656
uniprot
proteins
pubmed
9125146
uniprot
proteins
pubmed
9405250
uniprot
proteins
sequence_length
442
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasmic vesicle, autophagosome {ECO:0000250|UniProtKB:Q13501}. Preautophagosomal structure {ECO:0000250|UniProtKB:Q13501}. Cytoplasm, cytosol {ECO:0000269|PubMed:16286508, ECO:0000269|PubMed:22792322, ECO:0000269|PubMed:33397898}. Nucleus, PML body {ECO:0000250|UniProtKB:Q13501}. Late endosome {ECO:0000250|UniProtKB:Q13501}. Lysosome {ECO:0000250|UniProtKB:Q13501}. Nucleus {ECO:0000269|PubMed:16286508}. Endoplasmic reticulum {ECO:0000250|UniProtKB:Q13501}. Cytoplasm, myofibril, sarcomere {ECO:0000250|UniProtKB:O08623}. Note=In cardiac muscle, localizes to the sarcomeric band (By similarity). Localizes to cytoplasmic membraneless inclusion bodies, known as p62 bodies, containing polyubiquitinated protein aggregates (PubMed:20421418, PubMed:33397898). 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 (By similarity). Enriched in Rosenthal fibers of pilocytic astrocytoma (By similarity). In the cytoplasm, observed in both membrane-free ubiquitin-containing protein aggregates (sequestosomes) and membrane-surrounded autophagosomes (By similarity). Colocalizes with TRIM13 in the perinuclear endoplasmic reticulum (By similarity). Co-localizes with TRIM5 in cytoplasmic bodies (By similarity). When nuclear export is blocked by treatment with leptomycin B, accumulates in PML bodies (By similarity). {ECO:0000250|UniProtKB:O08623, ECO:0000250|UniProtKB:Q13501, ECO:0000269|PubMed:20421418, ECO:0000269|PubMed:33397898}.
uniprot
proteins