View source for Sequestosome 1

{{Infobox_gene}}
'''Sequestosome-1''' is a [[protein]] that in humans is encoded by the ''SQSTM1'' [[gene]].<ref name="pmid8650207">{{cite journal | vauthors = Joung I, Strominger JL, Shin J | title = Molecular cloning of a phosphotyrosine-independent ligand of the p56lck SH2 domain | journal = Proc Natl Acad Sci U S A | volume = 93 | issue = 12 | pages = 5991–5 | date = July 1996 | pmid = 8650207 | pmc = 39176 | doi = 10.1073/pnas.93.12.5991 }}</ref><ref name="pmid8551575">{{cite journal | vauthors = Devergne O, Hummel M, Koeppen H, Le Beau MM, Nathanson EC, Kieff E, Birkenbach M | title = A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes | journal = J Virol | volume = 70 | issue = 2 | pages = 1143–53 | date = February 1996 | pmid = 8551575 | pmc = 189923 | doi =  }}</ref><ref>{{cite web | title = Entrez Gene: SQSTM1 sequestosome 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8878| accessdate = }}</ref>  Also known as the '''ubiquitin-binding protein p62''',<ref>{{OMIM|601530}}</ref> it is an [[autophagosome]] cargo protein that targets other proteins that bind to it for selective [[autophagy]].  By interacting with [[GATA4]] and targeting it for degradation, it can inhibit GATA-4 associated [[senescence]] and senescence-associated secretory phenotype.<ref name="pmid26404812">{{cite journal | vauthors = Cassidy LD, Narita M | title = GATA get a hold on senescence | journal = Science | volume = 349 | issue = 6255 | pages = 1448–9 | year = 2015 | pmid = 26404812 | doi = 10.1126/science.aad2501 }}</ref>

== Model organisms ==

{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: right;" |
|+ ''Sqstm1'' knockout mouse phenotype
|-
! Characteristic!! Phenotype

|-
| [[Homozygote]] viability || bgcolor="#488ED3"|Normal
|-
| Fertility || bgcolor="#488ED3"|Normal
|-
| Body weight || bgcolor="#488ED3"|Normal
|-
| [[Open Field (animal test)|Anxiety]] || bgcolor="#488ED3"|Normal
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
|-
| Grip strength || bgcolor="#488ED3"|Normal
|-
| [[Hot plate test|Hot plate]] || bgcolor="#488ED3"|Normal
|-
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
|-
| [[Radiography]] || bgcolor="#488ED3"|Normal
|-
| Body temperature || bgcolor="#488ED3"|Normal
|-
| Eye morphology || bgcolor="#488ED3"|Normal
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
|-
| [[Haematology]] || bgcolor="#C40000"|Abnormal<ref name="Haematology">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MCGB/haematology-cbc/ |title=Haematology data for Sqstm1 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Peripheral blood lymphocyte]]s || bgcolor="#488ED3"|Normal
|-
| [[Micronucleus test]] || bgcolor="#488ED3"|Normal
|-
| Heart weight || bgcolor="#488ED3"|Normal
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Salmonella'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MCGB/salmonella-challenge/ |title=''Salmonella'' infection data for Sqstm1 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| ''[[Citrobacter]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Citrobacter'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MCGB/citrobacter-challenge/ |title=''Citrobacter'' infection data for Sqstm1 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| colspan=2; style="text-align: center;" | All tests and analysis from<ref name="mgp_reference">{{cite journal | doi = 10.1111/j.1755-3768.2010.4142.x | title = The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice | year = 2010 | author = Gerdin AK | journal = Acta Ophthalmologica | volume = 88 | pages =  925–7 }}</ref><ref>[http://www.sanger.ac.uk/mouseportal/ Mouse Resources Portal], Wellcome Trust Sanger Institute.</ref>
|}
[[Model organism]]s have been used in the study of SQSTM1 function. A conditional [[knockout mouse]] line, called ''Sqstm1<sup>tm1a(KOMP)Wtsi</sup>''<ref name="allele_ref">{{cite web |url=http://www.knockoutmouse.org/martsearch/search?query=Sqstm1 |title=International Knockout Mouse Consortium}}</ref><ref name="mgi_allele_ref">{{cite web |url=http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4364926 |title=Mouse Genome Informatics}}</ref> was generated as part of the [[International Knockout Mouse Consortium]] program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.<ref name="pmid21677750">{{cite journal | vauthors = Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–342 | year = 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | year = 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A Mouse for All Reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | year = 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref>

Male and female animals underwent a standardized [[phenotypic screen]] to determine the effects of deletion.<ref name="mgp_reference" /><ref name="pmid21722353">{{cite journal | vauthors = van der Weyden L, White JK, Adams DJ, Logan DW | title = The mouse genetics toolkit: revealing function and mechanism. | journal = Genome Biol | volume = 12 | issue = 6 | pages = 224 | year = 2011 | pmid = 21722353 | pmc = 3218837 | doi = 10.1186/gb-2011-12-6-224 }}</ref> Twenty two tests were carried out on [[homozygous]] [[mutant]] mice and one significant abnormality was observed: females had abnormal [[complete blood count]] parameters, including an increased [[red blood cell]] distribution width and increased mean [[platelet]] volume.<ref name="mgp_reference" />

== Interactions ==

Sequestosome 1 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[MAP1LC3A]],<ref name = "pmid18653543">{{cite journal | vauthors = Shvets E, Fass E, Scherz-Shouval R, Elazar Z | title = The N-terminus and Phe52 residue of LC3 recruit p62/SQSTM1 into autophagosomes | journal = J. Cell Sci. | volume = 121 | issue = Pt 16 | pages = 2685–95 | pmid = 18653543 | doi = 10.1242/jcs.026005 | date=August 2008}}</ref>
* [[PRKCI]],<ref name = pmid9566925>{{cite journal | vauthors = Sanchez P, De Carcer G, Sandoval IV, Moscat J, Diaz-Meco MT | title = Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62 | journal = Mol. Cell. Biol. | volume = 18 | issue = 5 | pages = 3069–80 | date = May 1998 | pmid = 9566925 | pmc = 110686 | doi =  10.1128/mcb.18.5.3069}}</ref> 
* [[RAD23A]],<ref name = pmid16189514>{{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 }}</ref> 
* [[RIPK1]],<ref name = "pmid10356400">{{cite journal | vauthors = Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT, Moscat J | title = The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation | journal = EMBO J. | volume = 18 | issue = 11 | pages = 3044–53 | pmid = 10356400 | pmc = 1171386 | doi = 10.1093/emboj/18.11.3044 }}</ref> 
* [[TRAF6]]<ref name = pmid10747026>{{cite journal | vauthors = Sanz L, Diaz-Meco MT, Nakano H, Moscat J | title = The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway | journal = EMBO J. | volume = 19 | issue = 7 | pages = 1576–86 | date = April 2000 | pmid = 10747026 | pmc = 310227 | doi = 10.1093/emboj/19.7.1576 }}</ref> 
* [[TrkA]],<ref name = pmid11244088>{{cite journal | vauthors = Wooten MW, Seibenhener ML, Mamidipudi V, Diaz-Meco MT, Barker PA, Moscat J | title = The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor | journal = J. Biol. Chem. | volume = 276 | issue = 11 | pages = 7709–12 | date = March 2001 | pmid = 11244088 | doi = 10.1074/jbc.C000869200 }}</ref><ref name = "pmid12471037">{{cite journal | vauthors = Geetha T, Wooten MW | title = Association of the atypical protein kinase C-interacting protein p62/ZIP with nerve growth factor receptor TrkA regulates receptor trafficking and Erk5 signaling | journal = J. Biol. Chem. | volume = 278 | issue = 7 | pages = 4730–9 | pmid = 12471037 | doi = 10.1074/jbc.M208468200 | date=February 2003}}</ref><ref name = "pmid18457658">{{cite journal | vauthors = Jadhav T, Geetha T, Jiang J, Wooten MW | title = Identification of a consensus site for TRAF6/p62 polyubiquitination | journal = Biochem. Biophys. Res. Commun. | volume = 371 | issue = 3 | pages = 521–4 | pmid = 18457658 | pmc = 2474794 | doi = 10.1016/j.bbrc.2008.04.138 }}</ref><ref name = "pmid18174161">{{cite journal | vauthors = Wooten MW, Geetha T, Babu JR, Seibenhener ML, Peng J, Cox N, Diaz-Meco MT, Moscat J | title = Essential role of sequestosome 1/p62 in regulating accumulation of Lys63-ubiquitinated proteins | journal = J. Biol. Chem. | volume = 283 | issue = 11 | pages = 6783–9 | pmid = 18174161 | doi = 10.1074/jbc.M709496200 | date=March 2008}}</ref>  and
* [[TrkB]].<ref name = pmid12471037/><ref name = pmid18457658/> 
* [[Nrf2]] <ref>Feng, Lifeng et al. “Tamoxifen activates Nrf2-dependent SQSTM1 transcription to promote endometrial hyperplasia” Theranostics vol. 7,7 1890-1900. 10 Apr. 2017, doi:10.7150/thno.19135</ref> {{Div col end}}

== References ==
{{Reflist}}

== Further reading ==
{{Refbegin | 2}}
* {{cite journal | vauthors = Geetha T, Wooten MW | title = Structure and functional properties of the ubiquitin binding protein p62 | journal = FEBS Lett. | volume = 512 | issue = 1–3 | pages = 19–24 | year = 2002 | pmid = 11852044 | doi = 10.1016/S0014-5793(02)02286-X }}
* {{cite journal | vauthors = Layfield R, Ciani B, Ralston SH, Hocking LJ, Sheppard PW, Searle MS, Cavey JR | title = Structural and functional studies of mutations affecting the UBA domain of SQSTM1 (p62) which cause Paget's disease of bone | journal = Biochem. Soc. Trans. | volume = 32 | issue = Pt 5 | pages = 728–30 | year = 2005 | pmid = 15493999 | doi = 10.1042/BST0320728 }}
* {{cite journal | vauthors = Michou L, Collet C, Laplanche JL, Orcel P, Cornélis F | title = Genetics of Paget's disease of bone | journal = Joint Bone Spine | volume = 73 | issue = 3 | pages = 243–8 | year = 2006 | pmid = 16574459 | doi = 10.1016/j.jbspin.2005.05.009 }}
* {{cite journal | vauthors = Park I, Chung J, Walsh CT, Yun Y, Strominger JL, Shin J | title = Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 92 | issue = 26 | pages = 12338–42 | year = 1996 | pmid = 8618896 | pmc = 40352 | doi = 10.1073/pnas.92.26.12338 }}
* {{cite journal | vauthors = Iyer N, Reagan MS, Wu KJ, Canagarajah B, Friedberg EC | title = Interactions involving the human RNA polymerase II transcription/nucleotide excision repair complex TFIIH, the nucleotide excision repair protein XPG, and Cockayne syndrome group B (CSB) protein | journal = Biochemistry | volume = 35 | issue = 7 | pages = 2157–67 | year = 1996 | pmid = 8652557 | doi = 10.1021/bi9524124 }}
* {{cite journal | vauthors = Vadlamudi RK, Joung I, Strominger JL, Shin J | title = p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins | journal = J. Biol. Chem. | volume = 271 | issue = 34 | pages = 20235–7 | year = 1996 | pmid = 8702753 | doi = 10.1074/jbc.271.34.20235 }}
* {{cite journal | vauthors = Marcus SL, Winrow CJ, Capone JP, Rachubinski RA | title = A p56(lck) ligand serves as a coactivator of an orphan nuclear hormone receptor | journal = J. Biol. Chem. | volume = 271 | issue = 44 | pages = 27197–200 | year = 1996 | pmid = 8910285 | doi = 10.1074/jbc.271.44.27197 }}
* {{cite journal | vauthors = Jallal B, Mossie K, Vasiloudis G, Knyazev P, Zachwieja J, Clairvoyant F, Schilling J, Ullrich A | title = The receptor-like protein-tyrosine phosphatase DEP-1 is constitutively associated with a 64-kDa protein serine/threonine kinase | journal = J. Biol. Chem. | volume = 272 | issue = 18 | pages = 12158–63 | year = 1997 | pmid = 9115287 | doi = 10.1074/jbc.272.18.12158 }}
* {{cite journal | vauthors = Sanchez P, De Carcer G, Sandoval IV, Moscat J, Diaz-Meco MT | title = Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62 | journal = Mol. Cell. Biol. | volume = 18 | issue = 5 | pages = 3069–80 | year = 1998 | pmid = 9566925 | pmc = 110686 | doi =  10.1128/mcb.18.5.3069}}
* {{cite journal | vauthors = Vadlamudi RK, Shin J | title = Genomic structure and promoter analysis of the p62 gene encoding a non-proteasomal multiubiquitin chain binding protein | journal = FEBS Lett. | volume = 435 | issue = 2–3 | pages = 138–42 | year = 1998 | pmid = 9762895 | doi = 10.1016/S0014-5793(98)01021-7 }}
* {{cite journal | vauthors = Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT, Moscat J | title = The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation | journal = EMBO J. | volume = 18 | issue = 11 | pages = 3044–53 | year = 1999 | pmid = 10356400 | pmc = 1171386 | doi = 10.1093/emboj/18.11.3044 }}
* {{cite journal | vauthors = Stumptner C, Heid H, Fuchsbichler A, Hauser H, Mischinger HJ, Zatloukal K, Denk H | title = Analysis of intracytoplasmic hyaline bodies in a hepatocellular carcinoma. Demonstration of p62 as major constituent | journal = Am. J. Pathol. | volume = 154 | issue = 6 | pages = 1701–10 | year = 1999 | pmid = 10362795 | pmc = 1866621 | doi = 10.1016/S0002-9440(10)65426-0 }}
* {{cite journal | vauthors = Sudo T, Maruyama M, Osada H | title = p62 functions as a p38 MAP kinase regulator | journal = Biochem. Biophys. Res. Commun. | volume = 269 | issue = 2 | pages = 521–5 | year = 2000 | pmid = 10708586 | doi = 10.1006/bbrc.2000.2333 }}
* {{cite journal | vauthors = Sanz L, Diaz-Meco MT, Nakano H, Moscat J | title = The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway | journal = EMBO J. | volume = 19 | issue = 7 | pages = 1576–86 | year = 2000 | pmid = 10747026 | pmc = 310227 | doi = 10.1093/emboj/19.7.1576 }}
* {{cite journal | vauthors = Wooten MW, Seibenhener ML, Mamidipudi V, Diaz-Meco MT, Barker PA, Moscat J | title = The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor | journal = J. Biol. Chem. | volume = 276 | issue = 11 | pages = 7709–12 | year = 2001 | pmid = 11244088 | doi = 10.1074/jbc.C000869200 }}
* {{cite journal | vauthors = Kuusisto E, Salminen A, Alafuzoff I | title = Ubiquitin-binding protein p62 is present in neuronal and glial inclusions in human tauopathies and synucleinopathies | journal = NeuroReport | volume = 12 | issue = 10 | pages = 2085–90 | year = 2001 | pmid = 11447312 | doi = 10.1097/00001756-200107200-00009 }}
* {{cite journal | vauthors = Laurin N, Brown JP, Lemainque A, Duchesne A, Huot D, Lacourcière Y, Drapeau G, Verreault J, Raymond V, Morissette J | title = Paget disease of bone: mapping of two loci at 5q35-qter and 5q31 | journal = Am. J. Hum. Genet. | volume = 69 | issue = 3 | pages = 528–43 | year = 2001 | pmid = 11473345 | pmc = 1235483 | doi = 10.1086/322975 }}
* {{cite journal | vauthors = Chang S, Kim JH, Shin J | title = p62 forms a ternary complex with PKCzeta and PAR-4 and antagonizes PAR-4-induced PKCzeta inhibition | journal = FEBS Lett. | volume = 510 | issue = 1–2 | pages = 57–61 | year = 2002 | pmid = 11755531 | doi = 10.1016/S0014-5793(01)03224-0 }}
* {{Feng, Lifeng et al. “Tamoxifen activates Nrf2-dependent SQSTM1 transcription to promote endometrial hyperplasia” Theranostics vol. 7,7 1890-1900. 10 Apr. 2017, doi:10.7150/thno.19135}}
{{Refend}}

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[[Category:Genes mutated in mice]]