ID:SQSTM_HUMAN DESCRIPTION: RecName: Full=Sequestosome-1; AltName: Full=EBI3-associated protein of 60 kDa; Short=EBIAP; Short=p60; AltName: Full=Phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa; AltName: Full=Ubiquitin-binding protein p62; FUNCTION: Adapter protein which binds ubiquitin and 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. 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 problably 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. Interacts with MAP1LC3A. INTERACTION: Self; NbExp=2; IntAct=EBI-307104, EBI-307104; P38182:ATG8 (xeno); NbExp=3; IntAct=EBI-307104, EBI-2684; O95166:GABARAP; NbExp=10; IntAct=EBI-307104, EBI-712001; Q9H0R8:GABARAPL1; NbExp=7; IntAct=EBI-307104, EBI-746969; P60520:GABARAPL2; NbExp=8; IntAct=EBI-307104, EBI-720116; Q14145:KEAP1; NbExp=8; IntAct=EBI-307104, EBI-751001; Q9Z2X8:Keap1 (xeno); NbExp=2; IntAct=EBI-307104, EBI-647110; Q9H492:MAP1LC3A; NbExp=5; IntAct=EBI-307104, EBI-720768; Q9GZQ8:MAP1LC3B; NbExp=12; IntAct=EBI-307104, EBI-373144; Q9BXW4:MAP1LC3C; NbExp=2; IntAct=EBI-307104, EBI-2603996; Q14596:NBR1; NbExp=5; IntAct=EBI-307104, EBI-742698; P54725:RAD23A; NbExp=2; IntAct=EBI-307104, EBI-746453; P84022:SMAD3; NbExp=3; IntAct=EBI-307104, EBI-347161; P12504:vif (xeno); NbExp=2; IntAct=EBI-307104, EBI-779991; SUBCELLULAR LOCATION: Cytoplasm. Late endosome. Nucleus. Endoplasmic reticulum. Note=Sarcomere (By similarity). In cardiac muscles localizes to the sarcomeric band (By similarity). Localizes to late endosomes. May also localize to the nucleus. Accumulates in neurofibrillary tangles and in Lewy bodies of neurons from individuals with Alzheimer and Parkinson disease respectively. Enriched in Rosenthal fibers of pilocytic astrocytoma. In liver cells, accumulates in Mallory bodies associated with alcoholic hepatitis, Wilson disease, indian childhood cirrhosis and in hyaline bodies associated with hepatocellular carcinoma. Colocalizes with TRIM13 in the perinuclear endoplasmic reticulum. TISSUE SPECIFICITY: Ubiquitously expressed. INDUCTION: By proteasomal inhibitor PSI and prostaglandin J2 (PGJ2) (at protein level). By phorbol 12-myristate 13-acetate (PMA). DOMAIN: The UBA domain binds specifically 'Lys-63'-linked polyubiquitin chains of polyubiquitinated substrates. Mediates the interaction with TRIM55. DOMAIN: The OPR domain mediates homooligomerization and interactions with PRKCZ, PRKCI, MAP2K5 and NBR1. DOMAIN: The ZZ-type zinc finger mediates the interaction with RIPK1. PTM: Phosphorylated. May be phosphorylated by PRKCZ (By similarity). Phosphorylated in vitro by TTN. DISEASE: Defects in SQSTM1 are a cause of Paget disease of bone (PDB) [MIM:602080]. PDB is a metabolic bone disease affecting the axial skeleton and characterized by focal areas of increased and disorganized bone turn-over due to activated osteoclasts. Manifestations of the disease include bone pain, deformity, pathological fractures, deafness, neurological complications and increased risk of osteosarcoma. PDB is a chronic disease affecting 2 to 3% of the population above the age of 40 years. SIMILARITY: Contains 1 OPR domain. SIMILARITY: Contains 1 UBA domain. SIMILARITY: Contains 1 ZZ-type zinc finger.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13501
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0000422 mitophagy GO:0000423 macromitophagy GO:0001934 positive regulation of protein phosphorylation GO:0002376 immune system process GO:0002931 response to ischemia GO:0006468 protein phosphorylation GO:0006511 ubiquitin-dependent protein catabolic process GO:0006914 autophagy GO:0006915 apoptotic process GO:0007032 endosome organization GO:0008104 protein localization GO:0010821 regulation of mitochondrion organization GO:0016197 endosomal transport GO:0016236 macroautophagy GO:0030154 cell differentiation GO:0035556 intracellular signal transduction GO:0035973 aggrephagy GO:0043065 positive regulation of apoptotic process GO:0043066 negative regulation of apoptotic process GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling GO:0044130 negative regulation of growth of symbiont in host GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0046578 regulation of Ras protein signal transduction GO:0051291 protein heterooligomerization GO:0061635 regulation of protein complex stability GO:0070498 interleukin-1-mediated signaling pathway GO:0098780 response to mitochondrial depolarisation GO:1900273 positive regulation of long-term synaptic potentiation GO:1903078 positive regulation of protein localization to plasma membrane GO:1905719 protein localization to perinuclear region of cytoplasm
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Common Gene Haplotype Alleles 
