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sequestosome-1; phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kD; ubiquitin-binding protein p62; EBI3-associated protein of 60 kD; p60; EBIAP (SQSTM1, ORCA, OSIL)

Function: 1) role in protein degradation 2) adapter protein 3) binds ubiquitin, polyubiquitin-binding protein 4) degraded by autophagy - autophagy suppresses tumorigenesis through elimination of SQSTM1 [4] 5) interacts with autophagic effector proteins LC3A & LC3B [1] & the related gamma-aminobutyrate receptor-associated protein 6) role in activation of transcription factor NF-kappa B - linked to extrinsic apoptosis pathway 7) activation of NFKB1 by TNF-alpha, NGF, IL1 8) titin downstream signaling in muscle cells 9) regulation of signaling cascades via ubiquitination 10) cell differentiation, apoptosis, immune response, regulation of K+ channels 11) interactions: PRKCI, PRKCZ, KCNAB1, GABRR1, GABRR2, GABRR3, EBI3, LCK, RASA1, PRKCZ, PRKCI, NR2F2, NTRK1,NTRK2, NTRK3, NBR1, MAP2K5, TRIM55, MAPKAPK5, PSMD4, PSMC2, RIPK1 K63-polyubiquitinated MAPT 12) forms ternary complexes with PRKCZ &KCNAB2 or PRKCZ & GABBR3 13) forms an NGF-induced complex with IKBKB, PRKCI, TRAF6 14) forms a complex with MAP2K5 & PRKCZ or PRKCI 15) forms complex with JUB, PRKCZ & TRAF6 16) forms ternary complex with PAWR & PRKCZ 17) phosphorylated by PRKCZ, TTN Structure: - homooligomer or heterooligomer - UBA domain binds specifically Lys-63-linked polyubiquitin chains of polyubiquitinated substrates & mediates the interaction with TRIM55 - OPR domain mediates homooligomerization & interactions with PRKCZ, PRKCI, MAP2K5, NBR1 - ZZ-type zinc finger mediates interaction with RIPK1 Compartment: - cytoplasm - in cardiac muscles localizes to sarcomeric band - localizes to late endosomes - may also localize to the nucleus Alternative splicing: Expression: - induction by proteasomal inhibitor PSI, prostaglandin J2, phorbol 12-myristate 13-acetate Pathology: - defects in SQSTM1 are a cause of Paget's disease of bone - accumulates in neurofibrillary tangles & in Lewy bodies of neurons from patients with Alzheimer's & Parkinson's disease, respectively - found in Rosenthal fibers of pilocytic astrocytoma - accumulates in Mallory bodies - accumulates in hyaline bodies associated with hepatocellular carcinoma

General

nuclear protein phosphoprotein zinc finger protein

Properties

SIZE: entity length = 440 aa MW = 48 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: LCK interaction {1-50} OPR {20-102} MOTIF: Ser phosphorylation site {S24} PRKCZ {43-107} MOTIF: PAWR interaction {50-80} GABRR3 interaction {122-224} MOTIF: Zn finger ZZ-type NAME: Zn finger ZZ-type SITE: 122-167 EFFECTOR-BOUND: Zn+2 Tyr phosphorylation site {Y148} binding site SITE: 170-220 FOR-BINDING-OF: LIM domain protein Ser phosphorylation site {S170} Ser phosphorylation site {S176} Ser phosphorylation site {S207} peptide motif {228-233} NTRK1 interaction {269-440} MOTIF: Thr phosphorylation site {T269} serine-rich region {272-294} MOTIF: serine residue (SEVERAL) Ser phosphorylation site {S272} Ser phosphorylation site {S276} Ser phosphorylation site {S328} Ser phosphorylation site {S332} Ser phosphorylation site {S355} Ser phosphorylation site {S361} Ser phosphorylation site {S365} Ser phosphorylation site {S366} UBA domain {389-434}

Database Correlations

OMIM correlations MORBIDMAP 601530 UniProt Q13501 PFAM correlations Entrez Gene 8878 Kegg hsa:8878

References

  1. UniProt :accession Q13501
  2. Pankiv S et al p62/SQSTM1 Binds Directly to Atg8/LC3 to Facilitate Degradation of Ubiquitinated Protein Aggregates by Autophagy J. Biol. Chem. 2007, 282:24131-2414 PMID: 17580304
  3. Ichimura Y Selective turnover of p62/A170/SQSTM1 by autophagy Autophagy. 2008 Nov 16;4(8):1063-6. PMID: 18776737
  4. Komatsu M et al Homeostatic Levels of p62 Control Cytoplasmic Inclusion Body Formation in Autophagy-Deficient Mice Cell 2007, 131:1149-1163 PMID: 18083104
  5. Mathew R et al Autophagy suppresses tumorigenesis through elimination of p62. Cell 2009, 137(6):1062-75 PMID: 19524509 - Moscat J et al p62 at the Crossroads of Autophagy, Apoptosis, and Cancer Cell 2009, 137:1001-1004 PMID: 19524504