Sequestosome

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Function

Sequestosome (SQS) or p62, is required for the formation and autophagic degredation of polyubiquitin-containg bodies. SQS may regulate signaling cascades through ubiquitination[1].

Structural highlights

SQS is a multi-domain protein. SQS domain structure includes:

  • PB1 domain which contains Phox and Berm1
  • ZZ-type zinc finger
  • SMIR – SOD interaction domain
  • TB – TRAF6 binding motif
  • LC3 – microtubule-associated protein 1 light chain 3B
  • LIR – interaction region
  • UBA – ubiquitin association domain.

Relevance

SQS is associated with fibrillary tangles in Alzheimer disease[2].

3D structures of sequestosome

Updated on 04-May-2025

Domains: PB1 1-102; ZZ 120-180; UBA 387-436

1q02, 2jy7, 2jy8, 2k0b, 2knv – hSQS UBA domain – human - NMR

6jm4 – hSQS-1 PB1 domain (mutant)
4uf8, 4uf9, 6tgy, 6th3 – hSQS-1 PB1 domain – Cryo EM
5yp7, 5yp8, 5ypa, 5ypb, 5ypc, 5ype, 5ypg, 5yph, 5ypi, 6miu – hSQS-1 ZZ domain
6mj7 – hSQS-1 ZZ domain + Arg
6khz – hSQS-1 ZZ domain + Gly
7r1o – hSQS-1 ZZ domain + drug
2ktr – rSQS PB1 domain – rat - NMR
2kkc – rSQS PB1 domain (mutant) - NMR
4mjs – hSQS-1 PB1 domain + protein kinase C zeta type
3b0f – mSQS UBA domain – mouse
2rru – mSQS UBA domain - NMR


Structure of human sequestosome UBA domain (PDB code 2jy8)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. Seibenhener ML, Babu JR, Geetha T, Wong HC, Krishna NR, Wooten MW. Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation. Mol Cell Biol. 2004 Sep;24(18):8055-68. PMID:15340068 doi:10.1128/MCB.24.18.8055-8068.2004
  2. Salminen A, Kaarniranta K, Haapasalo A, Hiltunen M, Soininen H, Alafuzoff I. Emerging role of p62/sequestosome-1 in the pathogenesis of Alzheimer's disease. Prog Neurobiol. 2012 Jan;96(1):87-95. doi: 10.1016/j.pneurobio.2011.11.005. Epub , 2011 Nov 22. PMID:22138392 doi:http://dx.doi.org/10.1016/j.pneurobio.2011.11.005

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Michal Harel