Sequestosome 1

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Identifiers
Aliases
External IDs	GeneCards: [1]
Orthologs
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a
Wikidata
View/Edit Human

Sequestosome-1 is a protein that in humans is encoded by the SQSTM1 gene. Also known as the ubiquitin-binding protein p62, 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.

Model organisms

Sqstm1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Abnormal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Salmonella infection	Normal
Citrobacter infection	Normal
All tests and analysis from

Model organisms have been used in the study of SQSTM1 function. A conditional knockout mouse line, called Sqstm1^{tm1a(KOMP)Wtsi} 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.

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. 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.

Interactions

Sequestosome 1 has been shown to interact with:

• MAP1LC3A,
• PRKCI,
• RAD23A,
• RIPK1,
• TRAF6
• TrkA, and
• TrkB.
• Nrf2

Further reading

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