Sequestosome 1 (SQSTM1)

OSIL; PDB3; ZIP3; p62; p62B; p60; A170; Paget Disease Of Bone 3; Oxidative Stress Induced Like; EBI3-associated protein of 60 kDa; Ubiquitin-binding protein p62

SPN	T584
HGNC	11280
MGI	107931
PubMed	22084127
RGD	69287
UniProt	Q13501
Wiki	Sequestosome_1

The Src homology type 2 (SH2) domain is a highly conserved motif of about 100 amino acids which mediates protein-protein interactions by binding to phosphotyrosine. p56-lck, a T-cell-specific src family tyrosine kinase with an SH2 domain, is involved in T-cell signal transduction. A 62-kD protein (Phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa) was identified by Park et al. (1995) as a ligand of the p56-lck SH2 domain. Gong et al. (1999) screened a yeast 2-hybrid library made from rat hippocampal mRNA against full-length Kv-beta-2 . Two previously unknown interacting proteins were identified, one of which was identical to Zip (PKC-zeta)-interacting protein), the rat homolog of p62. Zip1 and Zip2, which arise from alternative splicing, are identical except for 27 residues missing from Zip2.

Reference

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FEBS Lett. 435:138-142(1998) [PubMed] [Europe PMC] [Abstract]

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Am. J. Pathol. 154:1701-1710(1999) [PubMed] [Europe PMC] [Abstract]

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"p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins."
J. Biol. Chem. 271:20235-20237(1996) [PubMed] [Europe PMC] [Abstract]

"A p56(lck) ligand serves as a coactivator of an orphan nuclear hormone receptor."
J. Biol. Chem. 271:27197-27200(1996) [PubMed] [Europe PMC] [Abstract]

"Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62."
Mol. Cell. Biol. 18:3069-3080(1998) [PubMed] [Europe PMC] [Abstract]

"The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation."
EMBO J. 18:3044-3053(1999) [PubMed] [Europe PMC] [Abstract]

"p62 functions as a p38 MAP kinase regulator."
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"p62 Is a common component of cytoplasmic inclusions in protein aggregation diseases."
Am. J. Pathol. 160:255-263(2002) [PubMed] [Europe PMC] [Abstract]

"p62 forms a ternary complex with PKCzeta and PAR-4 and antagonizes PAR-4-induced PKCzeta inhibition."
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Hepatology 35:1053-1062(2002) [PubMed] [Europe PMC] [Abstract]

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"Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation."
Mol. Cell. Biol. 24:8055-8068(2004) [PubMed] [Europe PMC] [Abstract]

"The p62 scaffold regulates nerve growth factor-induced NF-kappaB activation by influencing TRAF6 polyubiquitination."
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"p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death."
J. Cell Biol. 171:603-614(2005) [PubMed] [Europe PMC] [Abstract]

"Sequestosome 1/p62 shuttles polyubiquitinated tau for proteasomal degradation."
J. Neurochem. 94:192-203(2005) [PubMed] [Europe PMC] [Abstract]

"The LIM protein Ajuba influences interleukin-1-induced NF-kappaB activation by affecting the assembly and activity of the protein kinase Czeta/p62/TRAF6 signaling complex."
Mol. Cell. Biol. 25:4010-4022(2005) [PubMed] [Europe PMC] [Abstract]

"Inhibition of sequestosome 1/p62 up-regulation prevents aggregation of ubiquitinated proteins induced by prostaglandin J2 without reducing its neurotoxicity."
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"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
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"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
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"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]

"p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy."
J. Biol. Chem. 282:24131-24145(2007) [PubMed] [Europe PMC] [Abstract]

"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
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"A quantitative atlas of mitotic phosphorylation."
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"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]

"p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy."
Autophagy 6:330-344(2010) [PubMed] [Europe PMC] [Abstract]

"Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance."
J. Cell Biol. 191:1159-1172(2010) [PubMed] [Europe PMC] [Abstract]

"p62/sequestosome-1 associates with and sustains the expression of retroviral restriction factor TRIM5alpha."
J. Virol. 84:5997-6006(2010) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
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"TRIM13 regulates ER stress induced autophagy and clonogenic ability of the cells."
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"TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death."
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"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
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"TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy."
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"The LIR motif - crucial for selective autophagy."
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"Structural determinants in GABARAP required for the selective binding and recruitment of ALFY to LC3B-positive structures."
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"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Structure of the ubiquitin-associated domain of p62 (SQSTM1) and implications for mutations that cause Paget's disease of bone."
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"Ubiquitin recognition by the ubiquitin-associated domain of p62 involves a novel conformational switch."
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"Conformation and dynamics of the three-helix bundle UBA domain of p62 from experiment and simulation."
Proteins 71:227-240(2008) [PubMed] [Europe PMC] [Abstract]

"Dimerisation of the UBA domain of p62 inhibits ubiquitin binding and regulates NF-kappaB signalling."
J. Mol. Biol. 396:178-194(2010) [PubMed] [Europe PMC] [Abstract]

"Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone."
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"Domain-specific mutations in sequestosome 1 (SQSTM1) cause familial and sporadic Paget's disease."
Hum. Mol. Genet. 11:2735-2739(2002) [PubMed] [Europe PMC] [Abstract]

"Three novel mutations in SQSTM1 identified in familial Paget's disease of bone."
J. Bone Miner. Res. 18:1748-1753(2003) [PubMed] [Europe PMC] [Abstract]

"Familial Paget's disease in The Netherlands: occurrence, identification of new mutations in the sequestosome 1 gene, and their clinical associations."
Arthritis Rheum. 50:1650-1654(2004) [PubMed] [Europe PMC] [Abstract]

"Identification of SQSTM1 mutations in familial Paget's disease in Australian pedigrees."
Bone 35:277-282(2004) [PubMed] [Europe PMC] [Abstract]

"Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB)."
J. Bone Miner. Res. 19:1013-1017(2004) [PubMed] [Europe PMC] [Abstract]

"Novel UBA domain mutations of SQSTM1 in Paget's disease of bone: genotype phenotype correlation, functional analysis, and structural consequences."
J. Bone Miner. Res. 19:1122-1127(2004) [PubMed] [Europe PMC] [Abstract]

"Detection and validation of non-synonymous coding SNPs from orthogonal analysis of shotgun proteomics data."
J. Proteome Res. 6:2331-2340(2007) [PubMed] [Europe PMC] [Abstract]