MGP Database

New search | Record Overview | Ontology/Pathway Information | Domain Information | UniProt Annotations | Related Proteins
MGP003729

UniProt Annotations

Entry Information
Gene Namesequestosome 1
Protein EntrySQSTM_HUMAN
UniProt IDQ13501
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q13501-1; Sequence=Displayed; Name=2; IsoId=Q13501-2; Sequence=VSP_015841;
DiseaseNote=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.
DiseasePaget disease of bone (PDB) [MIM:602080]: 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. {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}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins. {ECO:0000269|PubMed:23908376}.
DomainThe OPR domain mediates homooligomerization and interactions with FHOD3, MAP2K5, NBR1, PRKCI and PRKCZ. Both the OPR and UBA domains are necessary and sufficient for the localization into the ubiquitin-containing inclusion bodies.
DomainThe UBA domain binds specifically 'Lys-63'-linked polyubiquitin chains of polyubiquitinated substrates. Mediates the interaction with TRIM55. Both the UBA and OPR domains are necessary and sufficient for the localization into the ubiquitin- containing inclusion bodies.
DomainThe ZZ-type zinc finger mediates the interaction with RIPK1.
FunctionAutophagy receptor that interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family. Required both for the formation and autophagic degradation of polyubiquitin-containing bodies, called ALIS (aggresome-like induced structures) and links ALIS to the autophagic machinery. Involved in midbody ring degradation. 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. {ECO:0000250, 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:24128730}.
InductionBy proteasomal inhibitor PSI and prostaglandin J2 (PGJ2) (at protein level). By phorbol 12-myristate 13-acetate (PMA). {ECO:0000269|PubMed:12700667, ECO:0000269|PubMed:15911346, ECO:0000269|PubMed:9762895}.
InteractionSelf; NbExp=3; IntAct=EBI-307104, EBI-307104; P38182:ATG8 (xeno); NbExp=3; IntAct=EBI-307104, EBI-2684; O95817:BAG3; NbExp=3; IntAct=EBI-307104, EBI-747185; Q16543:CDC37; NbExp=3; IntAct=EBI-307104, EBI-295634; Q2V2M9:FHOD3; NbExp=6; IntAct=EBI-307104, EBI-6395541; Q2V2M9-4:FHOD3; NbExp=4; IntAct=EBI-307104, EBI-6395505; O95166:GABARAP; NbExp=10; IntAct=EBI-307104, EBI-712001; Q9H0R8:GABARAPL1; NbExp=7; IntAct=EBI-307104, EBI-746969; P60520:GABARAPL2; NbExp=12; IntAct=EBI-307104, EBI-720116; Q9Y6K9:IKBKG; NbExp=2; IntAct=EBI-307104, EBI-81279; Q14145:KEAP1; NbExp=8; IntAct=EBI-307104, EBI-751001; Q9Z2X8:Keap1 (xeno); NbExp=2; IntAct=EBI-307104, EBI-647110; Q9UDY8:MALT1; NbExp=2; IntAct=EBI-307104, EBI-1047372; Q9H492:MAP1LC3A; NbExp=7; IntAct=EBI-307104, EBI-720768; Q9GZQ8:MAP1LC3B; NbExp=15; IntAct=EBI-307104, EBI-373144; Q9BXW4:MAP1LC3C; NbExp=2; IntAct=EBI-307104, EBI-2603996; Q14596:NBR1; NbExp=6; IntAct=EBI-307104, EBI-742698; Q96CV9:OPTN; NbExp=7; IntAct=EBI-307104, EBI-748974; P41743:PRKCI; NbExp=5; IntAct=EBI-307104, EBI-286199; P54725:RAD23A; NbExp=2; IntAct=EBI-307104, EBI-746453; P58004:SESN2; NbExp=5; IntAct=EBI-307104, EBI-3939642; Q96B97:SH3KBP1; NbExp=4; IntAct=EBI-307104, EBI-346595; P84022:SMAD3; NbExp=3; IntAct=EBI-307104, EBI-347161; Q9Y4K3:TRAF6; NbExp=2; IntAct=EBI-307104, EBI-359276; P0CG48:UBC; NbExp=3; IntAct=EBI-307104, EBI-3390054; O70405:Ulk1 (xeno); NbExp=2; IntAct=EBI-307104, EBI-8390771; P12504:vif (xeno); NbExp=2; IntAct=EBI-307104, EBI-779991;
PtmPhosphorylated. May be phosphorylated by PRKCZ (By similarity). Phosphorylated in vitro by TTN. {ECO:0000250, ECO:0000269|PubMed:15592455, ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:16964243, ECO:0000269|PubMed:17081983, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:18691976, ECO:0000269|PubMed:19690332, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21406692}.
SimilarityContains 1 OPR domain. {ECO:0000305}.
SimilarityContains 1 UBA domain. {ECO:0000255|PROSITE- ProRule:PRU00212}.
SimilarityContains 1 ZZ-type zinc finger. {ECO:0000255|PROSITE- ProRule:PRU00228}.
Subcellular LocationCytoplasm. Late endosome. Lysosome. Cytoplasmic vesicle, autophagosome. Nucleus. Endoplasmic reticulum. Cytoplasm, P-body. Note=Sarcomere (By similarity). In cardiac muscles 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 the cytoplasmic bodies. {ECO:0000250}.
SubunitHomooligomer 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. 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. {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:21149568, ECO:0000269|PubMed:21923101, ECO:0000269|PubMed:22178386, ECO:0000269|PubMed:22421968, ECO:0000269|PubMed:24089205, ECO:0000269|PubMed:24668264, 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}.
Tissue SpecificityUbiquitously expressed. {ECO:0000269|PubMed:8650207}.
  logo