P62 (Ser28) (SQSTM1) Antibody – Rabbit Polyclonal

This gene encodes a multifunctional protein that binds ubiquitin and regulates activation of the nuclear factor kappa-B (NF-kB) signaling pathway. The protein functions as a scaffolding/adaptor protein in concert with TNF receptor-associated factor 6 to mediate activation of NF-kB in response to upstream signals. Alternatively spliced transcript variants encoding either the same or different isoforms have been identified for this gene. Mutations in this gene result in sporadic and familial Paget disease of bone. [provided by RefSeq, Mar 2009]

Function: Required both for the formation and autophagic degradation of polyubiquitin-containing bodies, called ALIS (aggresome-like induced structures). Links ALIS to the autophagic machinery via direct interaction with MAP1 LC3 family members. 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. Ref.12 Ref.14 Ref.15 Ref.19 Ref.24 Ref.25 Ref.26 Ref.27 Ref.29 Ref.31 Ref.53

Subunit structure: 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. 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. Ref.1 Ref.2 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24 Ref.26 Ref.27 Ref.28 Ref.31 Ref.34 Ref.40 Ref.41 Ref.44 Ref.46 Ref.47 Ref.49 Ref.51 Ref.53

Subcellular location: Cytoplasm. 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. Ref.7 Ref.11 Ref.13 Ref.16 Ref.18 Ref.19 Ref.23 Ref.26 Ref.27 Ref.41 Ref.44 Ref.46

Tissue specificity: Ubiquitously expressed. Ref.2

Induction: By proteasomal inhibitor PSI and prostaglandin J2 (PGJ2) (at protein level). By phorbol 12-myristate 13-acetate (PMA). Ref.6 Ref.22 Ref.29

Domain: The 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. Ref.14 Ref.20 Ref.21 Ref.24 Ref.26 Ref.27 Ref.31 Ref.50The 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. Ref.14 Ref.20 Ref.21 Ref.24 Ref.26 Ref.27 Ref.31 Ref.50The ZZ-type zinc finger mediates the interaction with RIPK1. Ref.14 Ref.20 Ref.21 Ref.24 Ref.26 Ref.27 Ref.31 Ref.50

Post-translational modification: Phosphorylated. May be phosphorylated by PRKCZ

By similarity. Phosphorylated in vitro by TTN. Ref.31

Involvement in disease: Paget 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.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.53 Ref.54 Ref.55 Ref.56 Ref.57 Ref.58 Ref.59 Ref.60In 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 polyubiquitinylated protein aggregates. Ref.26

Sequence similarities: Contains 1 OPR domain.Contains 1 UBA domain.Contains 1 ZZ-type zinc finger.