UniProt functional annotation for Q13501



	UniProt functional annotation for Q13501

UniProt code: Q13501.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Autophagy receptor required for selective macroautophagy (aggrephagy). Functions as a bridge between polyubiquitinated cargo and autophagosomes. Interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family (PubMed:16286508, PubMed:20168092, PubMed:24128730, PubMed:28404643, PubMed:22622177). Along with WDFY3, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures). Along with WDFY3, required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:24128730, PubMed:20168092). May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1. May play a role in titin/TTN downstream signaling in muscle cells. May regulate signaling cascades through ubiquitination. Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels. 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 (PubMed:27368102). Promotes relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (PubMed:29496741). Acts as an activator of the NFE2L2/NRF2 pathway via interaction with KEAP1: interaction inactivates the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective genes (PubMed:20452972, PubMed:28380357). {ECO:0000250|UniProtKB:O08623, ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10747026, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:12471037, ECO:0000269|PubMed:15340068, ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:15911346, ECO:0000269|PubMed:15953362, ECO:0000269|PubMed:16079148, ECO:0000269|PubMed:16286508, ECO:0000269|PubMed:19931284, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:24128730, ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:28380357, ECO:0000269|PubMed:28404643, ECO:0000269|PubMed:29496741}.

Subunit: Homooligomer or heterooligomer; may form homotypic arrays. Dimerization interferes with ubiquitin binding. Interacts directly with PRKCI and PRKCZ (Probable). Forms ternary complexes with PRKCZ and KCNAB2 or PRKCZ and GABBR3. Also interacts with KCNAB1, GABRR1, GABRR2 and GABRR3. Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6 (By similarity). Interacts with EBI3, LCK, RASA1, PRKCZ, PRKCI, NR2F2, NTRK1, NTRK2, NTRK3, NBR1, MAP2K5, TRIM13, TRIM55 and MAPKAPK5. Interacts with the proteasome subunits PSMD4 and PSMC2. Interacts with K63-polyubiquitinated MAPT/TAU. Interacts with IKBKB through PRKCZ and PRKCI. Interacts with NGFR through TRAF6 and bridges that complex to NTRK1. Forms a complex with MAP2K5 and PRKCZ or PRKCI. Component of a ternary complex with PAWR and PRKCZ. Upon TNF-alpha stimulation, interacts with RIPK1 probably bridging IKBKB to the TNF-R1 complex composed of TNF-R1/TNFRSF1A, TRADD and RIPK1. Forms a complex with JUB/Ajuba, PRKCZ and TRAF6. Interacts with TRAF6 and CYLD. 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. Directly interacts with MAP1LC3A and MAP1LC3B, as well as with other MAP1 LC3 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. Interacts with FHOD3. Interacts with TRMI5. 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 TRIM23 (PubMed:28871090). Interacts with LRRC25 (PubMed:29288164). Interacts with TRIM50 (PubMed:22792322). Interacts with TRIM16 (PubMed:30143514). Interacts with STING1; leading to relocalization of STING1 to autophagosomes. 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:20495340, PubMed:20452972). {ECO:0000250, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10708586, ECO:0000269|PubMed:10747026, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:11755531, ECO:0000269|PubMed:12471037, ECO:0000269|PubMed:12813044, ECO:0000269|PubMed:12887891, ECO:0000269|PubMed:15340068, ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:15870274, ECO:0000269|PubMed:15953362, ECO:0000269|PubMed:16286508, ECO:0000269|PubMed:17580304, ECO:0000269|PubMed:18083707, ECO:0000269|PubMed:19931284, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20357094, ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:20495340, ECO:0000269|PubMed:21149568, ECO:0000269|PubMed:21923101, ECO:0000269|PubMed:22178386, ECO:0000269|PubMed:22421968, ECO:0000269|PubMed:22792322, ECO:0000269|PubMed:23274085, ECO:0000269|PubMed:24089205, ECO:0000269|PubMed:24668264, ECO:0000269|PubMed:25040165, ECO:0000269|PubMed:25127057, ECO:0000269|PubMed:25422469, ECO:0000269|PubMed:28404643, ECO:0000269|PubMed:28871090, ECO:0000269|PubMed:29288164, ECO:0000269|PubMed:29496741, ECO:0000269|PubMed:30143514, ECO:0000269|PubMed:8551575, ECO:0000269|PubMed:8618896, ECO:0000269|PubMed:8650207, ECO:0000269|PubMed:8702753, ECO:0000269|PubMed:8910285, ECO:0000269|PubMed:9566925, ECO:0000305}.

Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:22792322}. Late endosome. Lysosome. Cytoplasmic vesicle, autophagosome. Nucleus. Endoplasmic reticulum. Nucleus, PML body {ECO:0000269|PubMed:20168092}. Cytoplasm, myofibril, sarcomere {ECO:0000250}. Note=In cardiac muscle, localizes to the sarcomeric band (By similarity). Commonly found in inclusion bodies containing polyubiquitinated protein aggregates. In neurodegenerative diseases, detected in Lewy bodies in Parkinson disease, neurofibrillary tangles in Alzheimer disease, and HTT aggregates in Huntington disease. 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. {ECO:0000269|PubMed:20168092}.

Tissue specificity: Ubiquitously expressed. {ECO:0000269|PubMed:8650207}.

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 feeback loop (PubMed:20452972). {ECO:0000269|PubMed:12700667, ECO:0000269|PubMed:15911346, ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:9762895}.

Domain: The UBA domain binds specifically 'Lys-63'-linked polyubiquitin chains of polyubiquitinated substrates. Mediates the interaction with TRIM55. Both the UBA and PB1 domains are necessary and sufficient for the localization into the ubiquitin-containing inclusion bodies. {ECO:0000269|PubMed:12857745, ECO:0000269|PubMed:15340068}.

Domain: The PB1 domain mediates homooligomerization and interactions with FHOD3, MAP2K5, NBR1, PRKCI, PRKCZ and WDR81. Both the PB1 and UBA domains are necessary and sufficient for the localization into the ubiquitin-containing inclusion bodies. {ECO:0000269|PubMed:12813044, ECO:0000269|PubMed:12887891, ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:28404643}.

Domain: The ZZ-type zinc finger mediates the interaction with RIPK1. {ECO:0000269|PubMed:10747026}.

Domain: The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins. {ECO:0000269|PubMed:23908376}.

Ptm: Phosphorylated. May be phosphorylated by PRKCZ (By similarity). Phosphorylated in vitro by TTN (PubMed:15802564). 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 MTOR promotes interaction with KEAP1 and inactivation of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes (By similarity). {ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:25040165, ECO:0000269|PubMed:29496741}.

Ptm: Ubiquitinated by RNF26: 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). 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). {ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:27880896, ECO:0000269|PubMed:28380357}.

Disease: Paget disease of bone 3 (PDB3) [MIM:167250]: A disorder of bone remodeling characterized by increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone. {ECO:0000269|PubMed:11992264, ECO:0000269|PubMed:12374763, ECO:0000269|PubMed:14584883, ECO:0000269|PubMed:15125799, ECO:0000269|PubMed:15146436, ECO:0000269|PubMed:15176995, ECO:0000269|PubMed:15207768, ECO:0000269|PubMed:19931284}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Note=In a cell model for Huntington disease (HD), appears to form a shell surrounding aggregates of mutant HTT that may protect cells from apoptosis, possibly by recruiting autophagosomal components to the polyubiquitinated protein aggregates. {ECO:0000269|PubMed:16286508}.

Disease: Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 (FTDALS3) [MIM:616437]: A neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. Some FTDALS3 patients may also develop Paget disease of bone. {ECO:0000269|PubMed:22084127, ECO:0000269|PubMed:24042580, ECO:0000269|PubMed:24899140, ECO:0000269|PubMed:25114083}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset (NADGP) [MIM:617145]: A neurodegenerative disorder characterized by gait abnormalities, ataxia, dysarthria, dystonia, vertical gaze palsy, and cognitive decline. Disease onset is in childhood or adolescence. NADGP transmission pattern is consistent with autosomal recessive inheritance. {ECO:0000269|PubMed:27545679}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Myopathy, distal, with rimmed vacuoles (DMRV) [MIM:617158]: An autosomal dominant myopathy with adult onset, characterized by muscle weakness of the distal upper and lower limbs, walking difficulties, and proximal weakness of the shoulder girdle muscles. Muscle biopsy shows rimmed vacuoles. {ECO:0000269|PubMed:26208961}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Note=A chromosomal aberration involving SQSTM1 is found in a form of acute lymphoblastic leukemia. Translocation t(5;9)(q35;q34) with NUP214. {ECO:0000269|PubMed:20851865}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Autophagy receptor required for selective macroautophagy (aggrephagy). Functions as a bridge between polyubiquitinated cargo and autophagosomes. Interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family (PubMed:16286508, PubMed:20168092, PubMed:24128730, PubMed:28404643, PubMed:22622177). Along with WDFY3, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures). Along with WDFY3, required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:24128730, PubMed:20168092). May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1. May play a role in titin/TTN downstream signaling in muscle cells. May regulate signaling cascades through ubiquitination. Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels. 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 (PubMed:27368102). Promotes relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (PubMed:29496741). Acts as an activator of the NFE2L2/NRF2 pathway via interaction with KEAP1: interaction inactivates the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective genes (PubMed:20452972, PubMed:28380357). {ECO:0000250\|UniProtKB:O08623, ECO:0000250\|UniProtKB:Q64337, ECO:0000269\|PubMed:10356400, ECO:0000269\|PubMed:10747026, ECO:0000269\|PubMed:11244088, ECO:0000269\|PubMed:12471037, ECO:0000269\|PubMed:15340068, ECO:0000269\|PubMed:15802564, ECO:0000269\|PubMed:15911346, ECO:0000269\|PubMed:15953362, ECO:0000269\|PubMed:16079148, ECO:0000269\|PubMed:16286508, ECO:0000269\|PubMed:19931284, ECO:0000269\|PubMed:20168092, ECO:0000269\|PubMed:20452972, ECO:0000269\|PubMed:22622177, ECO:0000269\|PubMed:24128730, ECO:0000269\|PubMed:27368102, ECO:0000269\|PubMed:28380357, ECO:0000269\|PubMed:28404643, ECO:0000269\|PubMed:29496741}.


Subunit:		Homooligomer or heterooligomer; may form homotypic arrays. Dimerization interferes with ubiquitin binding. Interacts directly with PRKCI and PRKCZ (Probable). Forms ternary complexes with PRKCZ and KCNAB2 or PRKCZ and GABBR3. Also interacts with KCNAB1, GABRR1, GABRR2 and GABRR3. Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6 (By similarity). Interacts with EBI3, LCK, RASA1, PRKCZ, PRKCI, NR2F2, NTRK1, NTRK2, NTRK3, NBR1, MAP2K5, TRIM13, TRIM55 and MAPKAPK5. Interacts with the proteasome subunits PSMD4 and PSMC2. Interacts with K63-polyubiquitinated MAPT/TAU. Interacts with IKBKB through PRKCZ and PRKCI. Interacts with NGFR through TRAF6 and bridges that complex to NTRK1. Forms a complex with MAP2K5 and PRKCZ or PRKCI. Component of a ternary complex with PAWR and PRKCZ. Upon TNF-alpha stimulation, interacts with RIPK1 probably bridging IKBKB to the TNF-R1 complex composed of TNF-R1/TNFRSF1A, TRADD and RIPK1. Forms a complex with JUB/Ajuba, PRKCZ and TRAF6. Interacts with TRAF6 and CYLD. 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. Directly interacts with MAP1LC3A and MAP1LC3B, as well as with other MAP1 LC3 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. Interacts with FHOD3. Interacts with TRMI5. 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 TRIM23 (PubMed:28871090). Interacts with LRRC25 (PubMed:29288164). Interacts with TRIM50 (PubMed:22792322). Interacts with TRIM16 (PubMed:30143514). Interacts with STING1; leading to relocalization of STING1 to autophagosomes. 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:20495340, PubMed:20452972). {ECO:0000250, ECO:0000269\|PubMed:10356400, ECO:0000269\|PubMed:10708586, ECO:0000269\|PubMed:10747026, ECO:0000269\|PubMed:11244088, ECO:0000269\|PubMed:11755531, ECO:0000269\|PubMed:12471037, ECO:0000269\|PubMed:12813044, ECO:0000269\|PubMed:12887891, ECO:0000269\|PubMed:15340068, ECO:0000269\|PubMed:15802564, ECO:0000269\|PubMed:15870274, ECO:0000269\|PubMed:15953362, ECO:0000269\|PubMed:16286508, ECO:0000269\|PubMed:17580304, ECO:0000269\|PubMed:18083707, ECO:0000269\|PubMed:19931284, ECO:0000269\|PubMed:20168092, ECO:0000269\|PubMed:20357094, ECO:0000269\|PubMed:20452972, ECO:0000269\|PubMed:20495340, ECO:0000269\|PubMed:21149568, ECO:0000269\|PubMed:21923101, ECO:0000269\|PubMed:22178386, ECO:0000269\|PubMed:22421968, ECO:0000269\|PubMed:22792322, ECO:0000269\|PubMed:23274085, ECO:0000269\|PubMed:24089205, ECO:0000269\|PubMed:24668264, ECO:0000269\|PubMed:25040165, ECO:0000269\|PubMed:25127057, ECO:0000269\|PubMed:25422469, ECO:0000269\|PubMed:28404643, ECO:0000269\|PubMed:28871090, ECO:0000269\|PubMed:29288164, ECO:0000269\|PubMed:29496741, ECO:0000269\|PubMed:30143514, ECO:0000269\|PubMed:8551575, ECO:0000269\|PubMed:8618896, ECO:0000269\|PubMed:8650207, ECO:0000269\|PubMed:8702753, ECO:0000269\|PubMed:8910285, ECO:0000269\|PubMed:9566925, ECO:0000305}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000269\|PubMed:20168092, ECO:0000269\|PubMed:22792322}. Late endosome. Lysosome. Cytoplasmic vesicle, autophagosome. Nucleus. Endoplasmic reticulum. Nucleus, PML body {ECO:0000269\|PubMed:20168092}. Cytoplasm, myofibril, sarcomere {ECO:0000250}. Note=In cardiac muscle, localizes to the sarcomeric band (By similarity). Commonly found in inclusion bodies containing polyubiquitinated protein aggregates. In neurodegenerative diseases, detected in Lewy bodies in Parkinson disease, neurofibrillary tangles in Alzheimer disease, and HTT aggregates in Huntington disease. 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. {ECO:0000269\|PubMed:20168092}.
Tissue specificity:		Ubiquitously expressed. {ECO:0000269\|PubMed:8650207}.
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 feeback loop (PubMed:20452972). {ECO:0000269\|PubMed:12700667, ECO:0000269\|PubMed:15911346, ECO:0000269\|PubMed:20452972, ECO:0000269\|PubMed:9762895}.
Domain:		The UBA domain binds specifically 'Lys-63'-linked polyubiquitin chains of polyubiquitinated substrates. Mediates the interaction with TRIM55. Both the UBA and PB1 domains are necessary and sufficient for the localization into the ubiquitin-containing inclusion bodies. {ECO:0000269\|PubMed:12857745, ECO:0000269\|PubMed:15340068}.
Domain:		The PB1 domain mediates homooligomerization and interactions with FHOD3, MAP2K5, NBR1, PRKCI, PRKCZ and WDR81. Both the PB1 and UBA domains are necessary and sufficient for the localization into the ubiquitin-containing inclusion bodies. {ECO:0000269\|PubMed:12813044, ECO:0000269\|PubMed:12887891, ECO:0000269\|PubMed:15802564, ECO:0000269\|PubMed:28404643}.
Domain:		The ZZ-type zinc finger mediates the interaction with RIPK1. {ECO:0000269\|PubMed:10747026}.
Domain:		The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins. {ECO:0000269\|PubMed:23908376}.
Ptm:		Phosphorylated. May be phosphorylated by PRKCZ (By similarity). Phosphorylated in vitro by TTN (PubMed:15802564). 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 MTOR promotes interaction with KEAP1 and inactivation of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes (By similarity). {ECO:0000250\|UniProtKB:Q64337, ECO:0000269\|PubMed:15802564, ECO:0000269\|PubMed:25040165, ECO:0000269\|PubMed:29496741}.
Ptm:		Ubiquitinated by RNF26: 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). 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). {ECO:0000269\|PubMed:27368102, ECO:0000269\|PubMed:27880896, ECO:0000269\|PubMed:28380357}.
Disease:		Paget disease of bone 3 (PDB3) [MIM:167250]: A disorder of bone remodeling characterized by increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone. {ECO:0000269\|PubMed:11992264, ECO:0000269\|PubMed:12374763, ECO:0000269\|PubMed:14584883, ECO:0000269\|PubMed:15125799, ECO:0000269\|PubMed:15146436, ECO:0000269\|PubMed:15176995, ECO:0000269\|PubMed:15207768, ECO:0000269\|PubMed:19931284}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Note=In a cell model for Huntington disease (HD), appears to form a shell surrounding aggregates of mutant HTT that may protect cells from apoptosis, possibly by recruiting autophagosomal components to the polyubiquitinated protein aggregates. {ECO:0000269\|PubMed:16286508}.
Disease:		Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 (FTDALS3) [MIM:616437]: A neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. Some FTDALS3 patients may also develop Paget disease of bone. {ECO:0000269\|PubMed:22084127, ECO:0000269\|PubMed:24042580, ECO:0000269\|PubMed:24899140, ECO:0000269\|PubMed:25114083}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset (NADGP) [MIM:617145]: A neurodegenerative disorder characterized by gait abnormalities, ataxia, dysarthria, dystonia, vertical gaze palsy, and cognitive decline. Disease onset is in childhood or adolescence. NADGP transmission pattern is consistent with autosomal recessive inheritance. {ECO:0000269\|PubMed:27545679}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Myopathy, distal, with rimmed vacuoles (DMRV) [MIM:617158]: An autosomal dominant myopathy with adult onset, characterized by muscle weakness of the distal upper and lower limbs, walking difficulties, and proximal weakness of the shoulder girdle muscles. Muscle biopsy shows rimmed vacuoles. {ECO:0000269\|PubMed:26208961}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Note=A chromosomal aberration involving SQSTM1 is found in a form of acute lymphoblastic leukemia. Translocation t(5;9)(q35;q34) with NUP214. {ECO:0000269\|PubMed:20851865}.