Sequestosome 1

SQSTM1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1Q02, 2JY7, 2JY8, 2K0B, 2KNV, 4MJS, 4UF8, 4UF9
Identifiers
Aliases	SQSTM1, A170, OSIL, PDB3, ZIP3, p60, p62, p62B, FTDALS3, Sequestosome 1, NADGP, DMRV
External IDs	OMIM: 601530; MGI: 107931; HomoloGene: 31202; GeneCards: SQSTM1; OMA:SQSTM1 - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q35.3 Start 179,806,398 bp End 179,838,078 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11|11 B1.3 Start 50,090,193 bp End 50,101,654 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right adrenal cortex left adrenal gland left adrenal cortex stromal cell of endometrium muscle of thigh right lobe of thyroid gland left lobe of thyroid gland gallbladder gastric mucosa Descending thoracic aorta Top expressed in dentate gyrus of hippocampal formation granule cell muscle of thigh right kidney triceps brachii muscle adrenal gland ventromedial nucleus superior frontal gyrus temporal muscle central gray substance of midbrain sternocleidomastoid muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein homodimerization activity receptor tyrosine kinase binding zinc ion binding SH2 domain binding metal ion binding protein serine/threonine kinase activity K63-linked polyubiquitin modification-dependent protein binding protein binding identical protein binding protein kinase binding protein kinase C binding ubiquitin binding enzyme binding ubiquitin protein ligase binding ionotropic glutamate receptor binding Cellular component cytoplasm endosome PML body late endosome P-body phagophore assembly site nucleoplasm aggresome autophagosome amphisome endoplasmic reticulum inclusion body lysosome sperm midpiece extracellular exosome cytoplasmic vesicle nucleus cytosol intracellular membrane-bounded organelle autolysosome mitochondrion sarcomere Lewy body Biological process apoptotic process protein localization cell differentiation positive regulation of protein phosphorylation intracellular signal transduction ubiquitin-dependent protein catabolic process regulation of mitochondrion organization protein heterooligomerization immune system process response to stress regulation of Ras protein signal transduction negative regulation of apoptotic process autophagy endosomal transport regulation of protein complex stability autophagy of mitochondrion positive regulation of apoptotic process regulation of I-kappaB kinase/NF-kappaB signaling positive regulation of transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II protein phosphorylation mitophagy response to mitochondrial depolarisation macroautophagy endosome organization protein localization to perinuclear region of cytoplasm response to ischemia mitochondrion organization aggrephagy selective autophagy interleukin-1-mediated signaling pathway positive regulation of long-term synaptic potentiation positive regulation of protein localization to plasma membrane Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8878 18412 Ensembl ENSG00000161011 ENSG00000284099 ENSMUSG00000015837 UniProt Q13501 Q64337 RefSeq (mRNA) NM_001142298 NM_001142299 NM_003900 NM_001290769 NM_011018 RefSeq (protein) NP_001135770 NP_001135771 NP_003891 NP_001277698 NP_035148 Location (UCSC) Chr 5: 179.81 – 179.84 Mb Chr 11: 50.09 – 50.1 Mb PubMed search
Wikidata
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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. S2CID 22029085.
• 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. S2CID 3184369.
• 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. S2CID 21272705.
• 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. S2CID 85579338.
• 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