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 17-May-2025

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

3b0f – mSQS UBA domain – mouse
2rru – mSQS UBA domain - NMR
2ktr – rSQS PB1 domain – rat - NMR
2kkc – rSQS PB1 domain (mutant) - NMR
3ade – mSQS + KEAP-1 – mouse
4mjs – hSQS-1 PB1 domain + protein kinase C zeta type
4uf8, 4uf9 – hSQS-1 PB1 domain – Cryo EM
5yp7, 5yp8, 5ypa, 5ypb, 5ypc, 5ype, 5ypg, 5yph, 5ypi – hSQS-1 residues 126-180


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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel