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Sequestosome

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+<StructureSection load='2jy8' size='340' side='right' caption='Structure of human sequestosome UBA domain (PDB code [[2jy8]])' scene=''>
-<StructureSection load='3ade' size='340' side='right' caption='Structure of mouse sequestosome complex with KEAP-1 (PDB code [[3ade]])' scene=''>
 == Function ==
+'''Sequestosome''' (SQS) or '''p62''', is required for the formation and autophagic degredation of polyubiquitin-containg bodies.  SQS may regulate signaling cascades through ubiquitination<ref>PMID:15340068</ref>.
-'''Sequestosome''' (SQS) or '''p62''', is required for the formation and autophagic degredation of polyubiquitin-containg bodies.  SQS may regulate signaling cascades through ubiquitination.
+== Structural highlights ==
 SQS is a multi-domain protein.  SQS domain structure includes: <br />
-PB1 domain which contains Phox and Berm1<br />
+*PB1 domain which contains Phox and Berm1<br />
-ZZ-type zinc finger <br />
+*ZZ-type zinc finger <br />
-SMIR – SOD interaction domain<br />
+*SMIR – SOD interaction domain<br />
-TB – TRAF6 binding motif<br />
+*TB – TRAF6 binding motif<br />
-LC3 – microtubule-associated protein 1 light chain 3B<br />
+*LC3 – microtubule-associated protein 1 light chain 3B<br />
-LIR – interaction region<br />
+*LIR – interaction region<br />
-UBA – ubiquitin association domain.
+*UBA – ubiquitin association domain.
-== Disease ==
 == Relevance ==
+SQS is associated with fibrillary tangles in Alzheimer disease<ref>PMID:22138392</ref>.
-== Structural highlights ==
 ==3D structures of sequestosome==
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 Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
-[[1q02]], [[2jy7]], [[2jy8]], [[2k0b]], [[2knv]] – SQS UBA domain – human - NMR<br />
+Domains: PB1 1-102; ZZ 120-180; UBA 387-436
-[[3b0p]] – mSQS UBA domain – mouse <br />
-[[2rru]] – mSQS UBA domain - NMR<br />
+[[1q02]], [[2jy7]], [[2jy8]], [[2k0b]], [[2knv]] – hSQS UBA domain – human - NMR<br />
+[[6jm4]] – hSQS-1 PB1 domain (mutant)<br />
+[[4uf8]], [[4uf9]], [[6tgy]], [[6th3]] – hSQS-1 PB1 domain – Cryo EM<br />
+[[5yp7]], [[5yp8]], [[5ypa]], [[5ypb]], [[5ypc]], [[5ype]], [[5ypg]], [[5yph]], [[5ypi]], [[6miu]] – hSQS-1 ZZ domain<br />
+[[6mj7]] – hSQS-1 ZZ domain + Arg<br />
+[[6khz]] – hSQS-1 ZZ domain + Gly<br />
+[[7r1o]] – hSQS-1 ZZ domain + drug<br />
 [[2ktr]] – rSQS PB1 domain – rat - NMR<br />
 [[2kkc]] – rSQS PB1 domain (mutant) - NMR<br />
-[[3ade]] – mSQS + KEAP-1 – mouse<br />
+[[4mjs]] – hSQS-1 PB1 domain + protein kinase C zeta type<br />
+[[3b0f]] – mSQS UBA domain – mouse <br />
+[[2rru]] – mSQS UBA domain - NMR<br />

Current revision

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

Show:Asymmetric Unit Biological Assembly

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1 Function
2 Structural highlights
3 Relevance
4 3D structures of sequestosome

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 15-November-2023

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

References

↑ 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
↑ 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