Sequestosome 1

Sequestosome-1 is a protein that in humans is encoded by the SQSTM1 gene.^[5][6][7] Also known as the ubiquitin-binding protein p62,^[8] 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.^[9]

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)[1] Band 5q35.3 Start 179,806,398 bp[1] End 179,838,078 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 B1.3 Start 50,090,193 bp[2] End 50,101,654 bp[2]
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 [3] [4]
Wikidata
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Mutations in SQSTM1 are a common cause of Paget's disease of bone.^[10]

Interactions

Sequestosome 1 has been shown to interact with:

• MAP1LC3A,^[11]
• PRKCI,^[12]
• RAD23A,^[13]
• RIPK1,^[14]
• TRAF6^[15]
• TrkA,^{[16][17][18][19]} and
• TrkB.^[17][18]
• Nrf2^[20]

Role in cancer

The SQSTM1 gene, which is actively transcribed as part of normal cellular function, is sometimes identified in fusion proteins, which can cause cancer when SQSTM1 is abnormally fused to a tyrosine kinase or other pro-proliferation gene. These genes are normally tightly regulated, but when bound to a minimally regulated gene like SQSTM1, they cause abnormal over-expression.^[21]