UniProtKB - Q13501 (SQSTM_HUMAN)
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- BLAST
>sp|Q13501|SQSTM_HUMAN Sequestosome-1 OS=Homo sapiens OX=9606 GN=SQSTM1 PE=1 SV=1 MASLTVKAYLLGKEDAAREIRRFSFCCSPEPEAEAEAAAGPGPCERLLSRVAALFPALRP GGFQAHYRDEDGDLVAFSSDEELTMAMSYVKDDIFRIYIKEKKECRRDHRPPCAQEAPRN MVHPNVICDGCNGPVVGTRYKCSVCPDYDLCSVCEGKGLHRGHTKLAFPSPFGHLSEGFS HSRWLRKVKHGHFGWPGWEMGPPGNWSPRPPRAGEARPGPTAESASGPSEDPSVNFLKNV GESVAAALSPLGIEVDIDVEHGGKRSRLTPVSPESSSTEEKSSSQPSSCCSDPSKPGGNV EGATQSLAEQMRKIALESEGRPEEQMESDNCSGGDDDWTHLSSKEVDPSTGELQSLQMPE SEGPSSLDPSQEGPTGLKEAALYPHLPPEADPRLIESLSQMLSMGFSDEGGWLTRLLQTK NYDIGAALDTIQYSKHPPPL
- Align
Protein
Sequestosome-1
Gene
SQSTM1
Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:
Annotation score:5 out of 5
<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>Select a section on the left to see content.
<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni
Autophagy receptor required for selective macroautophagy (aggrephagy). Functions as a bridge between polyubiquitinated cargo and autophagosomes. Interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family (PubMed:16286508, PubMed:20168092, PubMed:24128730, PubMed:28404643, PubMed:22622177). Along with WDFY3, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures). Along with WDFY3, required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:24128730, PubMed:20168092). May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1. May play a role in titin/TTN downstream signaling in muscle cells. May regulate signaling cascades through ubiquitination. Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). May be involved in cell differentiation, apoptosis, immune response and regulation of K+ channels. Involved in endosome organization by retaining vesicles in the perinuclear cloud: following ubiquitination by RNF26, attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport (PubMed:27368102).By similarity
<p>Manually curated information which has been propagated from a related experimentally characterized protein.</p> <p><a href="/manual/evidences#ECO:0000250">More...</a></p> Manual assertion inferred from sequence similarity toi
16 Publications<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More...</a></p> Manual assertion based on experiment ini
- Ref.12"The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation."
Sanz L., Sanchez P., Lallena M.-J., Diaz-Meco M.T., Moscat J.
EMBO J. 18:3044-3053(1999) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH RIPK1; PRKCZ; PRKCI; IKBKB; TRADD AND TNFRSF1A, FUNCTION. - Ref.14"The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway."
Sanz L., Diaz-Meco M.T., Nakano H., Moscat J.
EMBO J. 19:1576-1586(2000) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH TRAF6 AND RIPK1, DOMAIN, FUNCTION. - Ref.15"The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor."
Wooten M.W., Seibenhener M.L., Mamidipudi V., Diaz-Meco M.T., Barker P.A., Moscat J.
J. Biol. Chem. 276:7709-7712(2001) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH NTRK1; TRAF6; NGFR AND PRKCZ, FUNCTION. - Ref.19"Association of the atypical protein kinase C-interacting protein p62/ZIP with nerve growth factor receptor TrkA regulates receptor trafficking and Erk5 signaling."
Geetha T., Wooten M.W.
J. Biol. Chem. 278:4730-4739(2003) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH NTRK1; NTRK2 AND NTRK3, SUBCELLULAR LOCATION, FUNCTION. - Ref.24"Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation."
Seibenhener M.L., Babu J.R., Geetha T., Wong H.C., Krishna N.R., Wooten M.W.
Mol. Cell. Biol. 24:8055-8068(2004) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH TRAF6; PSMC2 AND PSMD4, DOMAIN, MUTAGENESIS OF LEU-398; PHE-406; LEU-413; LEU-417 AND ILE-431, FUNCTION. - Ref.25"The p62 scaffold regulates nerve growth factor-induced NF-kappaB activation by influencing TRAF6 polyubiquitination."
Wooten M.W., Geetha T., Seibenhener M.L., Babu J.R., Diaz-Meco M.T., Moscat J.
J. Biol. Chem. 280:35625-35629(2005) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION. - Ref.26"p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death."
Bjorkoy G., Lamark T., Brech A., Outzen H., Perander M., Overvatn A., Stenmark H., Johansen T.
J. Cell Biol. 171:603-614(2005) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, HOMOOLIGOMERIZATION, INTERACTION WITH MAP1LC3B, POSSIBLE PROTECTIVE ROLE IN HD, MUTAGENESIS OF ASP-69 AND ILE-431. - Ref.27"Sequestosome 1/p62 shuttles polyubiquitinated tau for proteasomal degradation."
Babu J.R., Geetha T., Wooten M.W.
J. Neurochem. 94:192-203(2005) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH MAPT, DOMAIN, SUBCELLULAR LOCATION, FUNCTION. - Ref.29"Inhibition of sequestosome 1/p62 up-regulation prevents aggregation of ubiquitinated proteins induced by prostaglandin J2 without reducing its neurotoxicity."
Wang Z., Figueiredo-Pereira M.E.
Mol. Cell. Neurosci. 29:222-231(2005) [PubMed] [Europe PMC] [Abstract]Cited for: INDUCTION, FUNCTION. - Ref.31"The kinase domain of titin controls muscle gene expression and protein turnover."
Lange S., Xiang F., Yakovenko A., Vihola A., Hackman P., Rostkova E., Kristensen J., Brandmeier B., Franzen G., Hedberg B., Gunnarsson L.G., Hughes S.M., Marchand S., Sejersen T., Richard I., Edstroem L., Ehler E., Udd B., Gautel M.
Science 308:1599-1603(2005) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH NBR1 AND TRIM55, PHOSPHORYLATION, DOMAINS, FUNCTION. - Ref.40"p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy."
Clausen T.H., Lamark T., Isakson P., Finley K., Larsen K.B., Brech A., Overvatn A., Stenmark H., Bjorkoy G., Simonsen A., Johansen T.
Autophagy 6:330-344(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH WDFY3, SUBCELLULAR LOCATION. - Ref.48"The deubiquitinating enzyme USP36 controls selective autophagy activation by ubiquitinated proteins."
Taillebourg E., Gregoire I., Viargues P., Jacomin A.C., Thevenon D., Faure M., Fauvarque M.O.
Autophagy 8:767-779(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION. - Ref.53"TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy."
Isakson P., Lystad A.H., Breen K., Koster G., Stenmark H., Simonsen A.
Autophagy 9:1955-1964(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION. - Ref.67"An ER-associated pathway defines endosomal architecture for controlled cargo transport."
Jongsma M.L., Berlin I., Wijdeven R.H., Janssen L., Janssen G.M., Garstka M.A., Janssen H., Mensink M., van Veelen P.A., Spaapen R.M., Neefjes J.
Cell 166:152-166(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, UBIQUITINATION. - Ref.71"The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy."
Liu X., Li Y., Wang X., Xing R., Liu K., Gan Q., Tang C., Gao Z., Jian Y., Luo S., Guo W., Yang C.
J. Cell Biol. 216:1301-1320(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH WDR81, DOMAIN. - Ref.76"Dimerisation of the UBA domain of p62 inhibits ubiquitin binding and regulates NF-kappaB signalling."
Long J., Garner T.P., Pandya M.J., Craven C.J., Chen P., Shaw B., Williamson M.P., Layfield R., Searle M.S.
J. Mol. Biol. 396:178-194(2010) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY NMR OF 387-436, SUBUNIT, FUNCTION, MUTAGENESIS OF GLU-409 AND GLY-410, CHARACTERIZATION OF VARIANT PDB3 ARG-425.
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Function’ section specifies the position(s) and type(s) of zinc fingers within the protein.<p><a href='/help/zn_fing' target='_top'>More...</a></p>Zinc fingeri | 122 – 167 | ZZ-typePROSITE-ProRule annotation <p>Manual validated information which has been generated by the UniProtKB automatic annotation system.</p> <p><a href="/manual/evidences#ECO:0000255">More...</a></p> Manual assertion according to rulesi Add BLAST | 46 |
<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni
- enzyme binding Source: UniProtKB <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ipi">GO evidence code guide</a></p> Inferred from physical interactioni
- identical protein binding Source: IntActInferred from physical interactioni
- ionotropic glutamate receptor binding Source: ARUK-UCL
- K63-linked polyubiquitin modification-dependent protein binding Source: UniProtKB <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayi
- protein homodimerization activity Source: Ensembl
- protein kinase binding Source: UniProtKBInferred from direct assayi
- protein kinase C binding Source: UniProtKBInferred from physical interactioni
- protein serine/threonine kinase activity Source: UniProtKB <p>Non-traceable Author Statement</p> <p>Used for statements in the abstract, introduction or discussion of a paper that cannot be traced back to another publication.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#nas">GO evidence code guide</a></p> Non-traceable author statementi
- receptor tyrosine kinase binding Source: ProtInc <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementi
- SH2 domain binding Source: UniProtKBInferred from direct assayi
- ubiquitin binding Source: UniProtKBInferred from direct assayi
- ubiquitin protein ligase binding Source: UniProtKBInferred from direct assayi
- zinc ion binding Source: InterPro
GO - Biological processi
- aggrephagy Source: UniProtKBInferred from physical interactioni
- apoptotic process Source: UniProtKB-KW
- autophagy Source: UniProtKB <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypei
- autophagy of mitochondrion Source: ParkinsonsUK-UCLNon-traceable author statementi
- cell differentiation Source: UniProtKB-KW
- endosomal transport Source: UniProtKBTraceable author statementi
- endosome organization Source: UniProtKBInferred from direct assayi
- immune system process Source: UniProtKB-KW
- interleukin-1-mediated signaling pathway Source: Reactome
- intracellular signal transduction Source: UniProtKBTraceable author statementi
- macroautophagy Source: GO_CentralInferred from mutant phenotypei
- mitochondrion organization Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestori
- mitophagy Source: ParkinsonsUK-UCL <p>Inferred from Genetic Interaction</p> <p>Used to describe “traditional” genetic interactions such as suppressors and synthetic lethals as well as other techniques such as functional complementation, rescue experiments, or inferences about a gene drawn from the phenotype of a mutation in a different gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#igi">GO evidence code guide</a></p> Inferred from genetic interactioni
- negative regulation of apoptotic process Source: Reactome
- negative regulation of growth of symbiont in host Source: Ensembl
- negative regulation of transcription by RNA polymerase II Source: Ensembl
- positive regulation of apoptotic process Source: Reactome
- positive regulation of long-term synaptic potentiation Source: ARUK-UCL
- positive regulation of protein localization to plasma membrane Source: ARUK-UCL
- positive regulation of protein phosphorylation Source: Ensembl
- positive regulation of transcription by RNA polymerase II Source: UniProtKBTraceable author statementi
- protein heterooligomerization Source: Ensembl
- protein localization Source: UniProtKBTraceable author statementi
- protein localization to perinuclear region of cytoplasm Source: UniProtKBInferred from direct assayi
- regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKBInferred from mutant phenotypei
- regulation of mitochondrion organization Source: ParkinsonsUK-UCLNon-traceable author statementi
- regulation of protein complex stability Source: UniProtKBInferred from direct assayi
- regulation of Ras protein signal transduction Source: UniProtKBNon-traceable author statementi
- response to ischemia Source: Ensembl
- response to mitochondrial depolarisation Source: ParkinsonsUK-UCLInferred from genetic interactioni
- selective autophagy Source: UniProtKBInferred from mutant phenotypei
- ubiquitin-dependent protein catabolic process Source: ProtIncTraceable author statementi
<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi
| Biological process | Apoptosis, Autophagy, Differentiation, Immunity |
| Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactome - a knowledgebase of biological pathways and processes More...Reactomei | R-HSA-205043 NRIF signals cell death from the nucleus R-HSA-209543 p75NTR recruits signalling complexes R-HSA-209560 NF-kB is activated and signals survival R-HSA-5205685 Pink/Parkin Mediated Mitophagy R-HSA-9020702 Interleukin-1 signaling |
SignaLink: a signaling pathway resource with multi-layered regulatory networks More...SignaLinki | Q13501 |
SIGNOR Signaling Network Open Resource More...SIGNORi | Q13501 |
Protein family/group databases
MoonDB Database of extreme multifunctional and moonlighting proteins More...MoonDBi | Q13501 Predicted |
<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi | Recommended name: Sequestosome-1Alternative name(s): EBI3-associated protein of 60 kDa Short name: EBIAP Short name: p60 Phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa Ubiquitin-binding protein p62 |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi | Name:SQSTM1 Synonyms:ORCA, OSIL |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>Organismi | Homo sapiens (Human) |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri | 9606 [NCBI] |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineagei | cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi |
|
Organism-specific databases
Eukaryotic Pathogen Database Resources More...EuPathDBi | HostDB:ENSG00000161011.19 |
Human Gene Nomenclature Database More...HGNCi | HGNC:11280 SQSTM1 |
Online Mendelian Inheritance in Man (OMIM) More...MIMi | 601530 gene |
neXtProt; the human protein knowledge platform More...neXtProti | NX_Q13501 |
<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi
Cytosol
- cytosol 2 Publications
Manual assertion based on experiment ini
- Ref.40"p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy."
Clausen T.H., Lamark T., Isakson P., Finley K., Larsen K.B., Brech A., Overvatn A., Stenmark H., Bjorkoy G., Simonsen A., Johansen T.
Autophagy 6:330-344(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH WDFY3, SUBCELLULAR LOCATION. - Ref.51"The E3-ubiquitin ligase TRIM50 interacts with HDAC6 and p62, and promotes the sequestration and clearance of ubiquitinated proteins into the aggresome."
Fusco C., Micale L., Egorov M., Monti M., D'Addetta E.V., Augello B., Cozzolino F., Calcagni A., Fontana A., Polishchuk R.S., Didelot G., Reymond A., Pucci P., Merla G.
PLoS ONE 7:E40440-E40440(2012) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH TRIM50, SUBCELLULAR LOCATION.
- cytosol 2 Publications
Endosome
Nucleus
- Nucleus
- PML body 1 Publication
Manual assertion based on experiment ini
- Ref.40"p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy."
Clausen T.H., Lamark T., Isakson P., Finley K., Larsen K.B., Brech A., Overvatn A., Stenmark H., Bjorkoy G., Simonsen A., Johansen T.
Autophagy 6:330-344(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH WDFY3, SUBCELLULAR LOCATION.
Endoplasmic reticulum
Lysosome
Other locations
- autophagosome
- sarcomere By similarity
Note: In cardiac muscle, localizes to the sarcomeric band (By similarity). Commonly found in inclusion bodies containing polyubiquitinated protein aggregates. In neurodegenerative diseases, detected in Lewy bodies in Parkinson disease, neurofibrillary tangles in Alzheimer disease, and HTT aggregates in Huntington disease. In protein aggregate diseases of the liver, found in large amounts in Mallory bodies of alcoholic and nonalcoholic steatohepatitis, hyaline bodies in hepatocellular carcinoma, and in SERPINA1 aggregates. Enriched in Rosenthal fibers of pilocytic astrocytoma. In the cytoplasm, observed in both membrane-free ubiquitin-containing protein aggregates (sequestosomes) and membrane-surrounded autophagosomes. Colocalizes with TRIM13 in the perinuclear endoplasmic reticulum. Co-localizes with TRIM5 in cytoplasmic bodies. When nuclear export is blocked by treatment with leptomycin B, accumulates in PML bodies.1 Publication- Ref.40"p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy."
Clausen T.H., Lamark T., Isakson P., Finley K., Larsen K.B., Brech A., Overvatn A., Stenmark H., Bjorkoy G., Simonsen A., Johansen T.
Autophagy 6:330-344(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH WDFY3, SUBCELLULAR LOCATION.
Manual assertion based on experiment ini
Cytosol
- cytosol Source: HPA
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB-SubCell
Endosome
- late endosome Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular exosome Source: UniProtKBInferred from high throughput direct assayi
Lysosome
- autolysosome Source: ParkinsonsUK-UCLInferred from direct assayi
Mitochondrion
- mitochondrion Source: Ensembl
Nucleus
- nucleoplasm Source: Reactome
- PML body Source: UniProtKBInferred from direct assayi
Other locations
- aggresome Source: GO_CentralInferred from biological aspect of ancestori
- amphisome Source: ParkinsonsUK-UCLInferred from direct assayi
- autophagosome Source: UniProtKBInferred from direct assayi
- cytoplasm Source: UniProtKBInferred from direct assayi
- inclusion body Source: UniProtKBInferred from direct assayi
- intracellular membrane-bounded organelle Source: HPA
- Lewy body Source: Ensembl
- P-body Source: UniProtKBInferred from direct assayi
- phagophore assembly site Source: Ensembl
- sarcomere Source: UniProtKB-SubCell
- sperm midpiece Source: Ensembl
Keywords - Cellular componenti
Cytoplasm, Cytoplasmic vesicle, Endoplasmic reticulum, Endosome, Lysosome, Nucleus<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi
<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei
Paget disease of bone 3 (PDB3)8 PublicationsManual assertion based on experiment ini
- Ref.76"Dimerisation of the UBA domain of p62 inhibits ubiquitin binding and regulates NF-kappaB signalling."
Long J., Garner T.P., Pandya M.J., Craven C.J., Chen P., Shaw B., Williamson M.P., Layfield R., Searle M.S.
J. Mol. Biol. 396:178-194(2010) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY NMR OF 387-436, SUBUNIT, FUNCTION, MUTAGENESIS OF GLU-409 AND GLY-410, CHARACTERIZATION OF VARIANT PDB3 ARG-425. - Ref.77"Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone."
Laurin N., Brown J.P., Morissette J., Raymond V.
Am. J. Hum. Genet. 70:1582-1588(2002) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PDB3 LEU-392, VARIANTS VAL-117 AND GLN-274. - Ref.78"Domain-specific mutations in sequestosome 1 (SQSTM1) cause familial and sporadic Paget's disease."
Hocking L.J., Lucas G.J.A., Daroszewska A., Mangion J., Olavesen M., Cundy T., Nicholson G.C., Ward L., Bennett S.T., Wuyts W., Van Hul W., Ralston S.H.
Hum. Mol. Genet. 11:2735-2739(2002) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PDB3 LEU-392. - Ref.79"Three novel mutations in SQSTM1 identified in familial Paget's disease of bone."
Johnson-Pais T.L., Wisdom J.H., Weldon K.S., Cody J.D., Hansen M.F., Singer F.R., Leach R.J.
J. Bone Miner. Res. 18:1748-1753(2003) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PDB3 LEU-387. - Ref.80"Familial Paget's disease in The Netherlands: occurrence, identification of new mutations in the sequestosome 1 gene, and their clinical associations."
Eekhoff E.W.M., Karperien M., Houtsma D., Zwinderman A.H., Dragoiescu C., Kneppers A.L.J., Papapoulos S.E.
Arthritis Rheum. 50:1650-1654(2004) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PDB3 LEU-392; PRO-399; THR-404 AND ARG-425. - Ref.81"Identification of SQSTM1 mutations in familial Paget's disease in Australian pedigrees."
Good D.A., Busfield F., Fletcher B.H., Lovelock P.K., Duffy D.L., Kesting J.B., Andersen J., Shaw J.T.E.
Bone 35:277-282(2004) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PDB3 LEU-392. - Ref.82"Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB)."
Falchetti A., Di Stefano M., Marini F., Del Monte F., Mavilia C., Strigoli D., De Feo M.L., Isaia G., Masi L., Amedei A., Cioppi F., Ghinoi V., Maddali Bongi S., Di Fede G., Sferrazza C., Rini G.B., Melchiorre D., Matucci-Cerinic M., Brandi M.L.
J. Bone Miner. Res. 19:1013-1017(2004) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PDB3 LEU-392; VAL-404 AND ARG-425. - Ref.83"Novel UBA domain mutations of SQSTM1 in Paget's disease of bone: genotype phenotype correlation, functional analysis, and structural consequences."
Hocking L.J., Lucas G.J.A., Daroszewska A., Cundy T., Nicholson G.C., Donath J., Walsh J.P., Finlayson C., Cavey J.R., Ciani B., Sheppard P.W., Searle M.S., Layfield R., Ralston S.H.
J. Bone Miner. Res. 19:1122-1127(2004) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PDB3 VAL-404; SER-411 AND ARG-425, CHARACTERIZATION OF VARIANTS VAL-404; SER-411 AND ARG-425.
Ref.76
"Dimerisation of the UBA domain of p62 inhibits ubiquitin binding and regulates NF-kappaB signalling."
Long J., Garner T.P., Pandya M.J., Craven C.J., Chen P., Shaw B., Williamson M.P., Layfield R., Searle M.S.
J. Mol. Biol. 396:178-194(2010) [PubMed] [Europe PMC] [Abstract]
Long J., Garner T.P., Pandya M.J., Craven C.J., Chen P., Shaw B., Williamson M.P., Layfield R., Searle M.S.
J. Mol. Biol. 396:178-194(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 387-436, SUBUNIT, FUNCTION, MUTAGENESIS OF GLU-409 AND GLY-410, CHARACTERIZATION OF VARIANT PDB3 ARG-425.
Ref.77
"Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone."
Laurin N., Brown J.P., Morissette J., Raymond V.
Am. J. Hum. Genet. 70:1582-1588(2002) [PubMed] [Europe PMC] [Abstract]
Laurin N., Brown J.P., Morissette J., Raymond V.
Am. J. Hum. Genet. 70:1582-1588(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PDB3 LEU-392, VARIANTS VAL-117 AND GLN-274.
Ref.78
"Domain-specific mutations in sequestosome 1 (SQSTM1) cause familial and sporadic Paget's disease."
Hocking L.J., Lucas G.J.A., Daroszewska A., Mangion J., Olavesen M., Cundy T., Nicholson G.C., Ward L., Bennett S.T., Wuyts W., Van Hul W., Ralston S.H.
Hum. Mol. Genet. 11:2735-2739(2002) [PubMed] [Europe PMC] [Abstract]
Hocking L.J., Lucas G.J.A., Daroszewska A., Mangion J., Olavesen M., Cundy T., Nicholson G.C., Ward L., Bennett S.T., Wuyts W., Van Hul W., Ralston S.H.
Hum. Mol. Genet. 11:2735-2739(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PDB3 LEU-392.
Ref.79
"Three novel mutations in SQSTM1 identified in familial Paget's disease of bone."
Johnson-Pais T.L., Wisdom J.H., Weldon K.S., Cody J.D., Hansen M.F., Singer F.R., Leach R.J.
J. Bone Miner. Res. 18:1748-1753(2003) [PubMed] [Europe PMC] [Abstract]
Johnson-Pais T.L., Wisdom J.H., Weldon K.S., Cody J.D., Hansen M.F., Singer F.R., Leach R.J.
J. Bone Miner. Res. 18:1748-1753(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PDB3 LEU-387.
Ref.80
"Familial Paget's disease in The Netherlands: occurrence, identification of new mutations in the sequestosome 1 gene, and their clinical associations."
Eekhoff E.W.M., Karperien M., Houtsma D., Zwinderman A.H., Dragoiescu C., Kneppers A.L.J., Papapoulos S.E.
Arthritis Rheum. 50:1650-1654(2004) [PubMed] [Europe PMC] [Abstract]
Eekhoff E.W.M., Karperien M., Houtsma D., Zwinderman A.H., Dragoiescu C., Kneppers A.L.J., Papapoulos S.E.
Arthritis Rheum. 50:1650-1654(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PDB3 LEU-392; PRO-399; THR-404 AND ARG-425.
Ref.81
"Identification of SQSTM1 mutations in familial Paget's disease in Australian pedigrees."
Good D.A., Busfield F., Fletcher B.H., Lovelock P.K., Duffy D.L., Kesting J.B., Andersen J., Shaw J.T.E.
Bone 35:277-282(2004) [PubMed] [Europe PMC] [Abstract]
Good D.A., Busfield F., Fletcher B.H., Lovelock P.K., Duffy D.L., Kesting J.B., Andersen J., Shaw J.T.E.
Bone 35:277-282(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PDB3 LEU-392.
Ref.82
"Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB)."
Falchetti A., Di Stefano M., Marini F., Del Monte F., Mavilia C., Strigoli D., De Feo M.L., Isaia G., Masi L., Amedei A., Cioppi F., Ghinoi V., Maddali Bongi S., Di Fede G., Sferrazza C., Rini G.B., Melchiorre D., Matucci-Cerinic M., Brandi M.L.
J. Bone Miner. Res. 19:1013-1017(2004) [PubMed] [Europe PMC] [Abstract]
Falchetti A., Di Stefano M., Marini F., Del Monte F., Mavilia C., Strigoli D., De Feo M.L., Isaia G., Masi L., Amedei A., Cioppi F., Ghinoi V., Maddali Bongi S., Di Fede G., Sferrazza C., Rini G.B., Melchiorre D., Matucci-Cerinic M., Brandi M.L.
J. Bone Miner. Res. 19:1013-1017(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PDB3 LEU-392; VAL-404 AND ARG-425.
Ref.83
"Novel UBA domain mutations of SQSTM1 in Paget's disease of bone: genotype phenotype correlation, functional analysis, and structural consequences."
Hocking L.J., Lucas G.J.A., Daroszewska A., Cundy T., Nicholson G.C., Donath J., Walsh J.P., Finlayson C., Cavey J.R., Ciani B., Sheppard P.W., Searle M.S., Layfield R., Ralston S.H.
J. Bone Miner. Res. 19:1122-1127(2004) [PubMed] [Europe PMC] [Abstract]
Hocking L.J., Lucas G.J.A., Daroszewska A., Cundy T., Nicholson G.C., Donath J., Walsh J.P., Finlayson C., Cavey J.R., Ciani B., Sheppard P.W., Searle M.S., Layfield R., Ralston S.H.
J. Bone Miner. Res. 19:1122-1127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PDB3 VAL-404; SER-411 AND ARG-425, CHARACTERIZATION OF VARIANTS VAL-404; SER-411 AND ARG-425.
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder of bone remodeling characterized by increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone.
See also OMIM:167250| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_023592 | 387 | P → L in PDB3 and FTDALS3. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_023593 | 392 | P → L in PDB3 and FTDALS3; no effect on polyubiquitin-binding. 9 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_023594 | 399 | S → P in PDB3. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_023595 | 404 | M → T in PDB3. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_023596 | 404 | M → V in PDB3; loss of polyubiquitin-binding. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_023597 | 411 | G → S in PDB3 and FTDALS3; no effect on polyubiquitin-binding. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_023598 | 425 | G → R in PDB3 and FTDALS3; loss of polyubiquitin-binding and increased activation of NF-kappa-B. 5 Publications Manual assertion based on experiment ini
| 1 |
In a cell model for Huntington disease (HD), appears to form a shell surrounding aggregates of mutant HTT that may protect cells from apoptosis, possibly by recruiting autophagosomal components to the polyubiquitinated protein aggregates.1 Publication
Manual assertion based on experiment ini
- Ref.26"p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death."
Bjorkoy G., Lamark T., Brech A., Outzen H., Perander M., Overvatn A., Stenmark H., Johansen T.
J. Cell Biol. 171:603-614(2005) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, HOMOOLIGOMERIZATION, INTERACTION WITH MAP1LC3B, POSSIBLE PROTECTIVE ROLE IN HD, MUTAGENESIS OF ASP-69 AND ILE-431.
Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 (FTDALS3)4 PublicationsManual assertion based on experiment ini
- Ref.44"SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis."
Fecto F., Yan J., Vemula S.P., Liu E., Yang Y., Chen W., Zheng J.G., Shi Y., Siddique N., Arrat H., Donkervoort S., Ajroud-Driss S., Sufit R.L., Heller S.L., Deng H.X., Siddique T.
Arch. Neurol. 68:1440-1446(2011) [PubMed] [Europe PMC] [Abstract]Cited for: INVOLVEMENT IN FTDALS3, VARIANTS FTDALS3 VAL-33; ILE-153; LEU-228; LYS-238 DEL; PRO-318; CYS-321; PRO-370; LEU-392; SER-411 AND ARG-425. - Ref.56"SQSTM1 mutations in French patients with frontotemporal dementia or frontotemporal dementia with amyotrophic lateral sclerosis."
French Clinical and Genetic Research Network on FTD/FTD-ALS
Le Ber I., Camuzat A., Guerreiro R., Bouya-Ahmed K., Bras J., Nicolas G., Gabelle A., Didic M., De Septenville A., Millecamps S., Lenglet T., Latouche M., Kabashi E., Campion D., Hannequin D., Hardy J., Brice A.
JAMA Neurol. 70:1403-1410(2013) [PubMed] [Europe PMC] [Abstract]Cited for: INVOLVEMENT IN FTDALS3, VARIANTS FTDALS3 VAL-33; VAL-381; LEU-387 AND LEU-392. - Ref.64"A phenotype of atypical apraxia of speech in a family carrying SQSTM1 mutation."
Boutoleau-Bretonniere C., Camuzat A., Le Ber I., Bouya-Ahmed K., Guerreiro R., Deruet A.L., Evrard C., Bras J., Lamy E., Auffray-Calvier E., Pallardy A., Hardy J., Brice A., Derkinderen P., Vercelletto M.
J. Alzheimers Dis. 43:625-630(2015) [PubMed] [Europe PMC] [Abstract]Cited for: INVOLVEMENT IN FTDALS3, VARIANT FTDALS3 LYS-238 DEL. - Ref.85"Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration."
van der Zee J., Van Langenhove T., Kovacs G.G., Dillen L., Deschamps W., Engelborghs S., Matej R., Vandenbulcke M., Sieben A., Dermaut B., Smets K., Van Damme P., Merlin C., Laureys A., Van Den Broeck M., Mattheijssens M., Peeters K., Benussi L. , Binetti G., Ghidoni R., Borroni B., Padovani A., Archetti S., Pastor P., Razquin C., Ortega-Cubero S., Hernandez I., Boada M., Ruiz A., de Mendonca A., Miltenberger-Miltenyi G., do Couto F.S., Sorbi S., Nacmias B., Bagnoli S., Graff C., Chiang H.H., Thonberg H., Perneczky R., Diehl-Schmid J., Alexopoulos P., Frisoni G.B., Bonvicini C., Synofzik M., Maetzler W., vom Hagen J.M., Schoels L., Haack T.B., Strom T.M., Prokisch H., Dols-Icardo O., Clarimon J., Lleo A., Santana I., Almeida M.R., Santiago B., Heneka M.T., Jessen F., Ramirez A., Sanchez-Valle R., Llado A., Gelpi E., Sarafov S., Tournev I., Jordanova A., Parobkova E., Fabrizi G.M., Testi S., Salmon E., Stroebel T., Santens P., Robberecht W., De Jonghe P., Martin J.J., Cras P., Vandenberghe R., De Deyn P.P., Cruts M., Sleegers K., Van Broeckhoven C.
Acta Neuropathol. 128:397-410(2014) [PubMed] [Europe PMC] [Abstract]Cited for: INVOLVEMENT IN FTDALS3, VARIANTS FTDALS3 VAL-16; VAL-33; GLU-80; MET-90; TRP-107; ASN-129; CYS-212; VAL-219; PRO-226; LEU-228; THR-232; LYS-238 DEL; ASN-258; CYS-321; GLY-329; LEU-348; LEU-387; LEU-392 AND PRO-430, VARIANTS VAL-17; ARG-103; GLN-107; TYR-108; HIS-110; VAL-117; SER-118; GLY-119; SER-125; CYS-139; ILE-153; LEU-180; HIS-217; GLU-238; 265-SER-ARG-266 DELINS SER-ARG; ASP-274; ILE-278; VAL-308; LYS-319; GLY-334 DEL; THR-349 AND LEU-439.
Ref.44
"SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis."
Fecto F., Yan J., Vemula S.P., Liu E., Yang Y., Chen W., Zheng J.G., Shi Y., Siddique N., Arrat H., Donkervoort S., Ajroud-Driss S., Sufit R.L., Heller S.L., Deng H.X., Siddique T.
Arch. Neurol. 68:1440-1446(2011) [PubMed] [Europe PMC] [Abstract]
Fecto F., Yan J., Vemula S.P., Liu E., Yang Y., Chen W., Zheng J.G., Shi Y., Siddique N., Arrat H., Donkervoort S., Ajroud-Driss S., Sufit R.L., Heller S.L., Deng H.X., Siddique T.
Arch. Neurol. 68:1440-1446(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN FTDALS3, VARIANTS FTDALS3 VAL-33; ILE-153; LEU-228; LYS-238 DEL; PRO-318; CYS-321; PRO-370; LEU-392; SER-411 AND ARG-425.
Ref.56
"SQSTM1 mutations in French patients with frontotemporal dementia or frontotemporal dementia with amyotrophic lateral sclerosis."
French Clinical and Genetic Research Network on FTD/FTD-ALS
Le Ber I., Camuzat A., Guerreiro R., Bouya-Ahmed K., Bras J., Nicolas G., Gabelle A., Didic M., De Septenville A., Millecamps S., Lenglet T., Latouche M., Kabashi E., Campion D., Hannequin D., Hardy J., Brice A.
JAMA Neurol. 70:1403-1410(2013) [PubMed] [Europe PMC] [Abstract]
French Clinical and Genetic Research Network on FTD/FTD-ALS
Le Ber I., Camuzat A., Guerreiro R., Bouya-Ahmed K., Bras J., Nicolas G., Gabelle A., Didic M., De Septenville A., Millecamps S., Lenglet T., Latouche M., Kabashi E., Campion D., Hannequin D., Hardy J., Brice A.
JAMA Neurol. 70:1403-1410(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN FTDALS3, VARIANTS FTDALS3 VAL-33; VAL-381; LEU-387 AND LEU-392.
Ref.64
"A phenotype of atypical apraxia of speech in a family carrying SQSTM1 mutation."
Boutoleau-Bretonniere C., Camuzat A., Le Ber I., Bouya-Ahmed K., Guerreiro R., Deruet A.L., Evrard C., Bras J., Lamy E., Auffray-Calvier E., Pallardy A., Hardy J., Brice A., Derkinderen P., Vercelletto M.
J. Alzheimers Dis. 43:625-630(2015) [PubMed] [Europe PMC] [Abstract]
Boutoleau-Bretonniere C., Camuzat A., Le Ber I., Bouya-Ahmed K., Guerreiro R., Deruet A.L., Evrard C., Bras J., Lamy E., Auffray-Calvier E., Pallardy A., Hardy J., Brice A., Derkinderen P., Vercelletto M.
J. Alzheimers Dis. 43:625-630(2015) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN FTDALS3, VARIANT FTDALS3 LYS-238 DEL.
Ref.85
"Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration."
van der Zee J., Van Langenhove T., Kovacs G.G., Dillen L., Deschamps W., Engelborghs S., Matej R., Vandenbulcke M., Sieben A., Dermaut B., Smets K., Van Damme P., Merlin C., Laureys A., Van Den Broeck M., Mattheijssens M., Peeters K., Benussi L. , Binetti G., Ghidoni R., Borroni B., Padovani A., Archetti S., Pastor P., Razquin C., Ortega-Cubero S., Hernandez I., Boada M., Ruiz A., de Mendonca A., Miltenberger-Miltenyi G., do Couto F.S., Sorbi S., Nacmias B., Bagnoli S., Graff C., Chiang H.H., Thonberg H., Perneczky R., Diehl-Schmid J., Alexopoulos P., Frisoni G.B., Bonvicini C., Synofzik M., Maetzler W., vom Hagen J.M., Schoels L., Haack T.B., Strom T.M., Prokisch H., Dols-Icardo O., Clarimon J., Lleo A., Santana I., Almeida M.R., Santiago B., Heneka M.T., Jessen F., Ramirez A., Sanchez-Valle R., Llado A., Gelpi E., Sarafov S., Tournev I., Jordanova A., Parobkova E., Fabrizi G.M., Testi S., Salmon E., Stroebel T., Santens P., Robberecht W., De Jonghe P., Martin J.J., Cras P., Vandenberghe R., De Deyn P.P., Cruts M., Sleegers K., Van Broeckhoven C.
Acta Neuropathol. 128:397-410(2014) [PubMed] [Europe PMC] [Abstract]
van der Zee J., Van Langenhove T., Kovacs G.G., Dillen L., Deschamps W., Engelborghs S., Matej R., Vandenbulcke M., Sieben A., Dermaut B., Smets K., Van Damme P., Merlin C., Laureys A., Van Den Broeck M., Mattheijssens M., Peeters K., Benussi L. , Binetti G., Ghidoni R., Borroni B., Padovani A., Archetti S., Pastor P., Razquin C., Ortega-Cubero S., Hernandez I., Boada M., Ruiz A., de Mendonca A., Miltenberger-Miltenyi G., do Couto F.S., Sorbi S., Nacmias B., Bagnoli S., Graff C., Chiang H.H., Thonberg H., Perneczky R., Diehl-Schmid J., Alexopoulos P., Frisoni G.B., Bonvicini C., Synofzik M., Maetzler W., vom Hagen J.M., Schoels L., Haack T.B., Strom T.M., Prokisch H., Dols-Icardo O., Clarimon J., Lleo A., Santana I., Almeida M.R., Santiago B., Heneka M.T., Jessen F., Ramirez A., Sanchez-Valle R., Llado A., Gelpi E., Sarafov S., Tournev I., Jordanova A., Parobkova E., Fabrizi G.M., Testi S., Salmon E., Stroebel T., Santens P., Robberecht W., De Jonghe P., Martin J.J., Cras P., Vandenberghe R., De Deyn P.P., Cruts M., Sleegers K., Van Broeckhoven C.
Acta Neuropathol. 128:397-410(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN FTDALS3, VARIANTS FTDALS3 VAL-16; VAL-33; GLU-80; MET-90; TRP-107; ASN-129; CYS-212; VAL-219; PRO-226; LEU-228; THR-232; LYS-238 DEL; ASN-258; CYS-321; GLY-329; LEU-348; LEU-387; LEU-392 AND PRO-430, VARIANTS VAL-17; ARG-103; GLN-107; TYR-108; HIS-110; VAL-117; SER-118; GLY-119; SER-125; CYS-139; ILE-153; LEU-180; HIS-217; GLU-238; 265-SER-ARG-266 DELINS SER-ARG; ASP-274; ILE-278; VAL-308; LYS-319; GLY-334 DEL; THR-349 AND LEU-439.
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. Some FTDALS3 patients may also develop Paget disease of bone.
See also OMIM:616437Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset (NADGP)1 PublicationManual assertion based on experiment ini
- Ref.66"Absence of the autophagy adaptor SQSTM1/p62 causes childhood-onset neurodegeneration with ataxia, dystonia, and gaze palsy."
Haack T.B., Ignatius E., Calvo-Garrido J., Iuso A., Isohanni P., Maffezzini C., Loennqvist T., Suomalainen A., Gorza M., Kremer L.S., Graf E., Hartig M., Berutti R., Paucar M., Svenningsson P., Stranneheim H., Brandberg G., Wedell A. , Kurian M.A., Hayflick S.A., Venco P., Tiranti V., Strom T.M., Dichgans M., Horvath R., Holinski-Feder E., Freyer C., Meitinger T., Prokisch H., Senderek J., Wredenberg A., Carroll C.J., Klopstock T.
Am. J. Hum. Genet. 99:735-743(2016) [PubMed] [Europe PMC] [Abstract]Cited for: INVOLVEMENT IN NADGP.
Ref.66
"Absence of the autophagy adaptor SQSTM1/p62 causes childhood-onset neurodegeneration with ataxia, dystonia, and gaze palsy."
Haack T.B., Ignatius E., Calvo-Garrido J., Iuso A., Isohanni P., Maffezzini C., Loennqvist T., Suomalainen A., Gorza M., Kremer L.S., Graf E., Hartig M., Berutti R., Paucar M., Svenningsson P., Stranneheim H., Brandberg G., Wedell A. , Kurian M.A., Hayflick S.A., Venco P., Tiranti V., Strom T.M., Dichgans M., Horvath R., Holinski-Feder E., Freyer C., Meitinger T., Prokisch H., Senderek J., Wredenberg A., Carroll C.J., Klopstock T.
Am. J. Hum. Genet. 99:735-743(2016) [PubMed] [Europe PMC] [Abstract]
Haack T.B., Ignatius E., Calvo-Garrido J., Iuso A., Isohanni P., Maffezzini C., Loennqvist T., Suomalainen A., Gorza M., Kremer L.S., Graf E., Hartig M., Berutti R., Paucar M., Svenningsson P., Stranneheim H., Brandberg G., Wedell A. , Kurian M.A., Hayflick S.A., Venco P., Tiranti V., Strom T.M., Dichgans M., Horvath R., Holinski-Feder E., Freyer C., Meitinger T., Prokisch H., Senderek J., Wredenberg A., Carroll C.J., Klopstock T.
Am. J. Hum. Genet. 99:735-743(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN NADGP.
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder characterized by gait abnormalities, ataxia, dysarthria, dystonia, vertical gaze palsy, and cognitive decline. Disease onset is in childhood or adolescence. NADGP transmission pattern is consistent with autosomal recessive inheritance.
See also OMIM:617145Myopathy, distal, with rimmed vacuoles (DMRV)1 PublicationManual assertion based on experiment ini
- Ref.65"SQSTM1 splice site mutation in distal myopathy with rimmed vacuoles."
Bucelli R.C., Arhzaouy K., Pestronk A., Pittman S.K., Rojas L., Sue C.M., Evilae A., Hackman P., Udd B., Harms M.B., Weihl C.C.
Neurology 85:665-674(2015) [PubMed] [Europe PMC] [Abstract]Cited for: INVOLVEMENT IN DMRV.
Ref.65
"SQSTM1 splice site mutation in distal myopathy with rimmed vacuoles."
Bucelli R.C., Arhzaouy K., Pestronk A., Pittman S.K., Rojas L., Sue C.M., Evilae A., Hackman P., Udd B., Harms M.B., Weihl C.C.
Neurology 85:665-674(2015) [PubMed] [Europe PMC] [Abstract]
Bucelli R.C., Arhzaouy K., Pestronk A., Pittman S.K., Rojas L., Sue C.M., Evilae A., Hackman P., Udd B., Harms M.B., Weihl C.C.
Neurology 85:665-674(2015) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN DMRV.
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant myopathy with adult onset, characterized by muscle weakness of the distal upper and lower limbs, walking difficulties, and proximal weakness of the shoulder girdle muscles. Muscle biopsy shows rimmed vacuoles.
See also OMIM:617158Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi | 7 | K → A: Loss of interactions with PRKCZ, PRCKI and NBR1. Loss of dimerization; when associated with A-69. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 9 | Y → F: No effect on interaction with LCK. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 13 | K → A: No effect on interaction with PRKCI. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 21 – 22 | RR → AA: Loss of interaction with PRKCI. Alters dimerization. 1 Publication Manual assertion based on experiment ini
| 2 | |
| Mutagenesisi | 67 | Y → A: No effect on interaction with PRKCZ. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 69 | D → A: No effect on interactions with PRKCZ, PRKCI and NBR1. Loss of localization in cytoplasmic inclusion bodies. Loss of dimerization; when associated with A-7. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 71 | D → A: No effect on interaction with PRKCI. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 73 | D → A: No effect on interactions with PRKCZ and PRKCI. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 80 | D → A: No effect on interaction with PRKCI. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 82 | E → A: No effect on interaction with PRKCI. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 323 – 324 | EE → AA: No effect on MAP1LC3B-binding. 1 Publication Manual assertion based on experiment ini
| 2 | |
| Mutagenesisi | 332 | S → A: No effect on MAP1LC3B-binding. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 335 – 337 | DDD → ADA: 75% decrease in MAP1LC3B-binding. 1 Publication Manual assertion based on experiment ini
| 3 | |
| Mutagenesisi | 338 | W → A: Strong decrease in MAP1LC3B-binding, disrupts interaction with GABARAP. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 342 | S → A: No effect on MAP1LC3B-binding. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 398 | L → V: No effect on polyubiquitin-binding. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 406 | F → V: Loss of polyubiquitin-binding. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 409 | E → K: Decreased activation of NF-kappa-B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 410 | G → K: Decreased activation of NF-kappa-B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 413 | L → V: No effect on polyubiquitin-binding. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 417 | L → V: Loss of polyubiquitin-binding. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Mutagenesisi | 431 | I → V: Partial loss of polyubiquitin-binding. Loss of localization to cytoplasmic inclusion bodies. 2 Publications Manual assertion based on experiment ini
| 1 |
Keywords - Diseasei
Amyotrophic lateral sclerosis, Disease mutation, NeurodegenerationOrganism-specific databases
DisGeNET More...DisGeNETi | 8878 |
MalaCards human disease database More...MalaCardsi | SQSTM1 |
| MIMi | 167250 phenotype 616437 phenotype 617145 phenotype 617158 phenotype |
Open Targets More...OpenTargetsi | ENSG00000161011 |
Orphanet; a database dedicated to information on rare diseases and orphan drugs More...Orphaneti | 803 Amyotrophic lateral sclerosis 275864 Behavioral variant of frontotemporal dementia 275872 Frontotemporal dementia with motor neuron disease 280110 NON RARE IN EUROPE: Paget disease of bone |
The Pharmacogenetics and Pharmacogenomics Knowledge Base More...PharmGKBi | PA36109 |
Polymorphism and mutation databases
BioMuta curated single-nucleotide variation and disease association database More...BioMutai | SQSTM1 |
Domain mapping of disease mutations (DMDM) More...DMDMi | 74735628 |
<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
|---|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methioninei | RemovedCombined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More...</a></p> Manual assertion inferred from combination of experimental and computational evidencei
| ||||
| <p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_0000072176 | 2 – 440 | Sequestosome-1Add BLAST | 439 | ||
| Isoform 2 (identifier: Q13501-2) | |||||
| Initiator methioninei | RemovedCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| ||||
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
|---|---|---|---|---|---|
| <p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei | 2 | N-acetylalanineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
| Modified residuei | 24 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
| Modified residuei | 148 | PhosphotyrosineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
| Modified residuei | 170 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
| Modified residuei | 176 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
| Modified residuei | 207 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
| Modified residuei | 233 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
| Modified residuei | 249 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
| Modified residuei | 266 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
| Modified residuei | 269 | PhosphothreonineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
| Modified residuei | 272 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
| Modified residuei | 306 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
| Modified residuei | 328 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
| Modified residuei | 332 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
| Modified residuei | 355 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
| Modified residuei | 361 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
| Modified residuei | 365 | PhosphoserineBy similarity Manual assertion inferred from sequence similarity toi | 1 | ||
| Modified residuei | 366 | PhosphoserineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
| Modified residuei | 403 | Phosphoserine; by ULK11 Publication Manual assertion based on experiment ini
| 1 | ||
| <p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki | 435 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources Manual assertion inferred from combination of experimental and computational evidencei
| |||
| Isoform 2 (identifier: Q13501-2) | |||||
| Modified residuei | 2 | N-acetylalanineCombined sources Manual assertion inferred from combination of experimental and computational evidencei
| 1 | ||
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi
Phosphorylated. May be phosphorylated by PRKCZ (By similarity). Phosphorylated in vitro by TTN. Phosphorylation at Ser-403 by ULK1 is stimulated by SESN2 (PubMed:25040165).By similarity2 Publications
Manual assertion based on experiment ini
- Ref.31"The kinase domain of titin controls muscle gene expression and protein turnover."
Lange S., Xiang F., Yakovenko A., Vihola A., Hackman P., Rostkova E., Kristensen J., Brandmeier B., Franzen G., Hedberg B., Gunnarsson L.G., Hughes S.M., Marchand S., Sejersen T., Richard I., Edstroem L., Ehler E., Udd B., Gautel M.
Science 308:1599-1603(2005) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH NBR1 AND TRIM55, PHOSPHORYLATION, DOMAINS, FUNCTION. - Ref.60"Sestrin2 promotes Unc-51-like kinase 1 mediated phosphorylation of p62/sequestosome-1."
Ro S.H., Semple I.A., Park H., Park H., Park H.W., Kim M., Kim J.S., Lee J.H.
FEBS J. 281:3816-3827(2014) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH SESN2 AND ULK1, PHOSPHORYLATION AT SER-403 BY ULK1.
Ubiquitinated by RNF26: ubiquitinated SQSTM1 attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport (PubMed:27368102). Deubiquitination by USP15 releases target vesicles for fast transport into the cell periphery (PubMed:27368102).1 Publication
Manual assertion based on experiment ini
- Ref.67"An ER-associated pathway defines endosomal architecture for controlled cargo transport."
Jongsma M.L., Berlin I., Wijdeven R.H., Janssen L., Janssen G.M., Garstka M.A., Janssen H., Mensink M., van Veelen P.A., Spaapen R.M., Neefjes J.
Cell 166:152-166(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, UBIQUITINATION.
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
Encyclopedia of Proteome Dynamics More...EPDi | Q13501 |
jPOST - Japan Proteome Standard Repository/Database More...jPOSTi | Q13501 |
MaxQB - The MaxQuant DataBase More...MaxQBi | Q13501 |
PaxDb, a database of protein abundance averages across all three domains of life More...PaxDbi | Q13501 |
PeptideAtlas More...PeptideAtlasi | Q13501 |
PRoteomics IDEntifications database More...PRIDEi | Q13501 |
ProteomicsDB human proteome resource More...ProteomicsDBi | 59496 59497 [Q13501-2] |
PTM databases
iPTMnet integrated resource for PTMs in systems biology context More...iPTMneti | Q13501 |
Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat. More...PhosphoSitePlusi | Q13501 |
SwissPalm database of S-palmitoylation events More...SwissPalmi | Q13501 |
<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni
<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi
Ubiquitously expressed.1 Publication
Manual assertion based on experiment ini
- Ref.2"Molecular cloning of a phosphotyrosine-independent ligand of the p56lck SH2 domain."
Joung I., Strominger J.L., Shin J.
Proc. Natl. Acad. Sci. U.S.A. 93:5991-5995(1996) [PubMed] [Europe PMC] [Abstract]
<p>This subsection of the ‘Expression’ section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni
By proteasomal inhibitor PSI and prostaglandin J2 (PGJ2) (at protein level). By phorbol 12-myristate 13-acetate (PMA).3 Publications
Manual assertion based on experiment ini
- Ref.6"Genomic structure and promoter analysis of the p62 gene encoding a non-proteasomal multiubiquitin chain binding protein."
Vadlamudi R.K., Shin J.
FEBS Lett. 435:138-142(1998) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-72, INDUCTION. - Ref.22"p62 overexpression in breast tumors and regulation by prostate-derived Ets factor in breast cancer cells."
Thompson H.G.R., Harris J.W., Wold B.J., Lin F., Brody J.P.
Oncogene 22:2322-2333(2003) [PubMed] [Europe PMC] [Abstract]Cited for: INDUCTION. - Ref.29"Inhibition of sequestosome 1/p62 up-regulation prevents aggregation of ubiquitinated proteins induced by prostaglandin J2 without reducing its neurotoxicity."
Wang Z., Figueiredo-Pereira M.E.
Mol. Cell. Neurosci. 29:222-231(2005) [PubMed] [Europe PMC] [Abstract]Cited for: INDUCTION, FUNCTION.
Gene expression databases
Bgee dataBase for Gene Expression Evolution More...Bgeei | ENSG00000161011 Expressed in 238 organ(s), highest expression level in left adrenal gland cortex |
CleanEx database of gene expression profiles More...CleanExi | HS_SQSTM1 |
ExpressionAtlas, Differential and Baseline Expression More...ExpressionAtlasi | Q13501 baseline and differential |
Genevisible search portal to normalized and curated expression data from Genevestigator More...Genevisiblei | Q13501 HS |
Organism-specific databases
Human Protein Atlas More...HPAi | CAB004587 HPA064165 HPA068843 |
<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni
<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei
Homooligomer or heterooligomer; may form homotypic arrays. Dimerization interferes with ubiquitin binding. Interacts directly with PRKCI and PRKCZ (Probable). Forms ternary complexes with PRKCZ and KCNAB2 or PRKCZ and GABBR3. Also interacts with KCNAB1, GABRR1, GABRR2 and GABRR3. Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6 (By similarity). Interacts with EBI3, LCK, RASA1, PRKCZ, PRKCI, NR2F2, NTRK1, NTRK2, NTRK3, NBR1, MAP2K5, TRIM13, TRIM55 and MAPKAPK5. Interacts with the proteasome subunits PSMD4 and PSMC2. Interacts with K63-polyubiquitinated MAPT/TAU. Interacts with IKBKB through PRKCZ and PRKCI. Interacts with NGFR through TRAF6 and bridges that complex to NTRK1. Forms a complex with MAP2K5 and PRKCZ or PRKCI. Component of a ternary complex with PAWR and PRKCZ. Upon TNF-alpha stimulation, interacts with RIPK1 probably bridging IKBKB to the TNF-R1 complex composed of TNF-R1/TNFRSF1A, TRADD and RIPK1. Forms a complex with JUB/Ajuba, PRKCZ and TRAF6. Interacts with TRAF6 and CYLD. Identified in a complex with TRAF6 and CYLD (By similarity). Identified in a heterotrimeric complex with ubiquitin and ZFAND5, where ZFAND5 and SQSTM1 both interact with the same ubiquitin molecule. Directly interacts with MAP1LC3A and MAP1LC3B, as well as with other MAP1 LC3 family members, including GABARAP, GABARAPL1 and GABARAPL2; these interactions are necessary for the recruitment MAP1 LC3 family members to inclusion bodies containing polyubiquitinated protein aggregates and for their degradation by autophagy. Interacts with FHOD3. Interacts with TRMI5. Interacts with SESN1 (PubMed:23274085). Interacts with SESN2 (PubMed:23274085, PubMed:25040165). Interacts with ULK1 (PubMed:25040165). Interacts with UBD (PubMed:25422469). Interacts with WDR81; the interaction is direct and regulates the interaction of SQSTM1 with ubiquitinated proteins (PubMed:28404643). Interacts with WDFY3; this interaction is required to recruit WDFY3 to cytoplasmic bodies and to PML bodies (PubMed:20168092). Interacts with TRIM23 (PubMed:28871090). Interacts with LRRC25 (PubMed:29288164). Interacts with TRIM50 (PubMed:22792322). Interacts with TRIM16 (PubMed:30143514).By similarityCurated39 Publications
Manual assertion based on experiment ini
- Ref.1"A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes."
Devergne O., Hummel M., Koeppen H., Le Beau M.M., Nathanson E.C., Kieff E., Birkenbach M.
J. Virol. 70:1143-1153(1996) [PubMed] [Europe PMC] [Abstract] - Ref.2"Molecular cloning of a phosphotyrosine-independent ligand of the p56lck SH2 domain."
Joung I., Strominger J.L., Shin J.
Proc. Natl. Acad. Sci. U.S.A. 93:5991-5995(1996) [PubMed] [Europe PMC] [Abstract] - Ref.8"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."
Park I., Chung J., Walsh C.T., Yun Y., Strominger J.L., Shin J.
Proc. Natl. Acad. Sci. U.S.A. 92:12338-12342(1995) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH LCK AND RASA1. - Ref.9"p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins."
Vadlamudi R.K., Joung I., Strominger J.L., Shin J.
J. Biol. Chem. 271:20235-20237(1996) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH UBIQUITIN. - Ref.10"A p56(lck) ligand serves as a coactivator of an orphan nuclear hormone receptor."
Marcus S.L., Winrow C.J., Capone J.P., Rachubinski R.A.
J. Biol. Chem. 271:27197-27200(1996) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH NR2F2. - Ref.11"Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62."
Sanchez P., De Carcer G., Sandoval I.V., Moscat J., Diaz-Meco M.T.
Mol. Cell. Biol. 18:3069-3080(1998) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH PRKCI AND PRKCZ, SUBCELLULAR LOCATION. - Ref.12"The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation."
Sanz L., Sanchez P., Lallena M.-J., Diaz-Meco M.T., Moscat J.
EMBO J. 18:3044-3053(1999) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH RIPK1; PRKCZ; PRKCI; IKBKB; TRADD AND TNFRSF1A, FUNCTION. - Ref.13"p62 functions as a p38 MAP kinase regulator."
Sudo T., Maruyama M., Osada H.
Biochem. Biophys. Res. Commun. 269:521-525(2000) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH MAPKAPK5, SUBCELLULAR LOCATION. - Ref.14"The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway."
Sanz L., Diaz-Meco M.T., Nakano H., Moscat J.
EMBO J. 19:1576-1586(2000) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH TRAF6 AND RIPK1, DOMAIN, FUNCTION. - Ref.15"The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor."
Wooten M.W., Seibenhener M.L., Mamidipudi V., Diaz-Meco M.T., Barker P.A., Moscat J.
J. Biol. Chem. 276:7709-7712(2001) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH NTRK1; TRAF6; NGFR AND PRKCZ, FUNCTION. - Ref.17"p62 forms a ternary complex with PKCzeta and PAR-4 and antagonizes PAR-4-induced PKCzeta inhibition."
Chang S., Kim J.H., Shin J.
FEBS Lett. 510:57-61(2002) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH PAWR AND PRKCZ. - Ref.19"Association of the atypical protein kinase C-interacting protein p62/ZIP with nerve growth factor receptor TrkA regulates receptor trafficking and Erk5 signaling."
Geetha T., Wooten M.W.
J. Biol. Chem. 278:4730-4739(2003) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH NTRK1; NTRK2 AND NTRK3, SUBCELLULAR LOCATION, FUNCTION. - Ref.20"Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins."
Lamark T., Perander M., Outzen H., Kristiansen K., Oevervatn A., Michaelsen E., Bjoerkoey G., Johansen T.
J. Biol. Chem. 278:34568-34581(2003) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH PRKCI; PRKCZ; MAP2K5 AND NBR1, DOMAIN, MUTAGENESIS OF LYS-7; LYS-13; 21-ARG-ARG-22; TYR-67; ASP-69; ASP-71; ASP-73; ASP-80 AND GLU-82, DIMERIZATION. - Ref.21"PB1 domain-mediated heterodimerization in NADPH oxidase and signaling complexes of atypical protein kinase C with Par6 and p62."
Wilson M.I., Gill D.J., Perisic O., Quinn M.T., Williams R.L.
Mol. Cell 12:39-50(2003) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH PRKCZ, DOMAIN, OLIGOMERIZATION, MUTAGENESIS OF LYS-7; ASP-69 AND ASP-73. - Ref.24"Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation."
Seibenhener M.L., Babu J.R., Geetha T., Wong H.C., Krishna N.R., Wooten M.W.
Mol. Cell. Biol. 24:8055-8068(2004) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH TRAF6; PSMC2 AND PSMD4, DOMAIN, MUTAGENESIS OF LEU-398; PHE-406; LEU-413; LEU-417 AND ILE-431, FUNCTION. - Ref.26"p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death."
Bjorkoy G., Lamark T., Brech A., Outzen H., Perander M., Overvatn A., Stenmark H., Johansen T.
J. Cell Biol. 171:603-614(2005) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, HOMOOLIGOMERIZATION, INTERACTION WITH MAP1LC3B, POSSIBLE PROTECTIVE ROLE IN HD, MUTAGENESIS OF ASP-69 AND ILE-431. - Ref.27"Sequestosome 1/p62 shuttles polyubiquitinated tau for proteasomal degradation."
Babu J.R., Geetha T., Wooten M.W.
J. Neurochem. 94:192-203(2005) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH MAPT, DOMAIN, SUBCELLULAR LOCATION, FUNCTION. - Ref.28"The LIM protein Ajuba influences interleukin-1-induced NF-kappaB activation by affecting the assembly and activity of the protein kinase Czeta/p62/TRAF6 signaling complex."
Feng Y., Longmore G.D.
Mol. Cell. Biol. 25:4010-4022(2005) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH AJUBA AND LIMD1. - Ref.31"The kinase domain of titin controls muscle gene expression and protein turnover."
Lange S., Xiang F., Yakovenko A., Vihola A., Hackman P., Rostkova E., Kristensen J., Brandmeier B., Franzen G., Hedberg B., Gunnarsson L.G., Hughes S.M., Marchand S., Sejersen T., Richard I., Edstroem L., Ehler E., Udd B., Gautel M.
Science 308:1599-1603(2005) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH NBR1 AND TRIM55, PHOSPHORYLATION, DOMAINS, FUNCTION. - Ref.34"p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy."
Pankiv S., Clausen T.H., Lamark T., Brech A., Bruun J.A., Outzen H., Overvatn A., Bjorkoy G., Johansen T.
J. Biol. Chem. 282:24131-24145(2007) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH GABARAP; GABARAPL1; GABARAPL2; MAP1LC3A AND MAP1LC3B, MUTAGENESIS OF 323-GLU-GLU-324; SER-332; 335-ASP--ASP-337; TRP-338 AND SER-342. - Ref.40"p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy."
Clausen T.H., Lamark T., Isakson P., Finley K., Larsen K.B., Brech A., Overvatn A., Stenmark H., Bjorkoy G., Simonsen A., Johansen T.
Autophagy 6:330-344(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH WDFY3, SUBCELLULAR LOCATION. - Ref.41"Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance."
Iskratsch T., Lange S., Dwyer J., Kho A.L., dos Remedios C., Ehler E.
J. Cell Biol. 191:1159-1172(2010) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH FHOD3. - Ref.42"p62/sequestosome-1 associates with and sustains the expression of retroviral restriction factor TRIM5alpha."
O'Connor C., Pertel T., Gray S., Robia S.L., Bakowska J.C., Luban J., Campbell E.M.
J. Virol. 84:5997-6006(2010) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH TRIM5, SUBCELLULAR LOCATION. - Ref.46"Independent interactions of ubiquitin-binding domains in a ubiquitin-mediated ternary complex."
Garner T.P., Strachan J., Shedden E.C., Long J.E., Cavey J.R., Shaw B., Layfield R., Searle M.S.
Biochemistry 50:9076-9087(2011) [PubMed] [Europe PMC] [Abstract]Cited for: IDENTIFICATION IN A COMPLEX WITH ZFAND5 AND UBIQUITIN, SUBCELLULAR LOCATION. - Ref.49"TRIM13 regulates ER stress induced autophagy and clonogenic ability of the cells."
Tomar D., Singh R., Singh A.K., Pandya C.D., Singh R.
Biochim. Biophys. Acta 1823:316-326(2012) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH TRIM13, SUBCELLULAR LOCATION. - Ref.50"TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death."
Seillier M., Peuget S., Gayet O., Gauthier C., N'guessan P., Monte M., Carrier A., Iovanna J.L., Dusetti N.J.
Cell Death Differ. 19:1525-1535(2012) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH MAP1LC3A. - Ref.51"The E3-ubiquitin ligase TRIM50 interacts with HDAC6 and p62, and promotes the sequestration and clearance of ubiquitinated proteins into the aggresome."
Fusco C., Micale L., Egorov M., Monti M., D'Addetta E.V., Augello B., Cozzolino F., Calcagni A., Fontana A., Polishchuk R.S., Didelot G., Reymond A., Pucci P., Merla G.
PLoS ONE 7:E40440-E40440(2012) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH TRIM50, SUBCELLULAR LOCATION. - Ref.54"Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage."
Bae S.H., Sung S.H., Oh S.Y., Lim J.M., Lee S.K., Park Y.N., Lee H.E., Kang D., Rhee S.G.
Cell Metab. 17:73-84(2013) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH SESN1 AND SESN2. - Ref.58"Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites."
Tang Z., Lin M.G., Stowe T.R., Chen S., Zhu M., Stearns T., Franco B., Zhong Q.
Nature 502:254-257(2013) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH MAP1LC3B. - Ref.59"TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition."
Mandell M.A., Jain A., Arko-Mensah J., Chauhan S., Kimura T., Dinkins C., Silvestri G., Munch J., Kirchhoff F., Simonsen A., Wei Y., Levine B., Johansen T., Deretic V.
Dev. Cell 30:394-409(2014) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH TRIM5. - Ref.60"Sestrin2 promotes Unc-51-like kinase 1 mediated phosphorylation of p62/sequestosome-1."
Ro S.H., Semple I.A., Park H., Park H., Park H.W., Kim M., Kim J.S., Lee J.H.
FEBS J. 281:3816-3827(2014) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH SESN2 AND ULK1, PHOSPHORYLATION AT SER-403 BY ULK1. - Ref.61"Structural determinants in GABARAP required for the selective binding and recruitment of ALFY to LC3B-positive structures."
Lystad A.H., Ichimura Y., Takagi K., Yang Y., Pankiv S., Kanegae Y., Kageyama S., Suzuki M., Saito I., Mizushima T., Komatsu M., Simonsen A.
EMBO Rep. 15:557-565(2014) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH GABARAP, MUTAGENESIS OF TRP-338. - Ref.63"Disruption of FAT10-MAD2 binding inhibits tumor progression."
Theng S.S., Wang W., Mah W.C., Chan C., Zhuo J., Gao Y., Qin H., Lim L., Chong S.S., Song J., Lee C.G.
Proc. Natl. Acad. Sci. U.S.A. 111:E5282-E5291(2014) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH UBD. - Ref.69"TRIM16 controls assembly and degradation of protein aggregates by modulating the p62-NRF2 axis and autophagy."
Jena K.K., Kolapalli S.P., Mehto S., Nath P., Das B., Sahoo P.K., Ahad A., Syed G.H., Raghav S.K., Senapati S., Chauhan S., Chauhan S.
EMBO J. 37:0-0(2018) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH TRIM16. - Ref.71"The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy."
Liu X., Li Y., Wang X., Xing R., Liu K., Gan Q., Tang C., Gao Z., Jian Y., Luo S., Guo W., Yang C.
J. Cell Biol. 216:1301-1320(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH WDR81, DOMAIN. - Ref.72"TRIM23 mediates virus-induced autophagy via activation of TBK1."
Sparrer K.M.J., Gableske S., Zurenski M.A., Parker Z.M., Full F., Baumgart G.J., Kato J., Pacheco-Rodriguez G., Liang C., Pornillos O., Moss J., Vaughan M., Gack M.U.
Nat. Microbiol. 2:1543-1557(2017) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH TRIM23. - Ref.74"Ubiquitin recognition by the ubiquitin-associated domain of p62 involves a novel conformational switch."
Long J., Gallagher T.R., Cavey J.R., Sheppard P.W., Ralston S.H., Layfield R., Searle M.S.
J. Biol. Chem. 283:5427-5440(2008) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY NMR OF 387-436, INTERACTION WITH UBIQUITIN. - Ref.76"Dimerisation of the UBA domain of p62 inhibits ubiquitin binding and regulates NF-kappaB signalling."
Long J., Garner T.P., Pandya M.J., Craven C.J., Chen P., Shaw B., Williamson M.P., Layfield R., Searle M.S.
J. Mol. Biol. 396:178-194(2010) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY NMR OF 387-436, SUBUNIT, FUNCTION, MUTAGENESIS OF GLU-409 AND GLY-410, CHARACTERIZATION OF VARIANT PDB3 ARG-425.
<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi
GO - Molecular functioni
- enzyme binding Source: UniProtKBInferred from physical interactioni
- identical protein binding Source: IntActInferred from physical interactioni
- ionotropic glutamate receptor binding Source: ARUK-UCL
- K63-linked polyubiquitin modification-dependent protein binding Source: UniProtKBInferred from direct assayi
- protein homodimerization activity Source: Ensembl
- protein kinase binding Source: UniProtKBInferred from direct assayi
- protein kinase C binding Source: UniProtKBInferred from physical interactioni
- receptor tyrosine kinase binding Source: ProtIncTraceable author statementi
- SH2 domain binding Source: UniProtKBInferred from direct assayi
- ubiquitin binding Source: UniProtKBInferred from direct assayi
- ubiquitin protein ligase binding Source: UniProtKBInferred from direct assayi
Protein-protein interaction databases
The Biological General Repository for Interaction Datasets (BioGrid) More...BioGridi | 114397, 309 interactors |
CORUM comprehensive resource of mammalian protein complexes More...CORUMi | Q13501 |
Database of interacting proteins More...DIPi | DIP-34443N |
The Eukaryotic Linear Motif resource for Functional Sites in Proteins More...ELMi | Q13501 |
Protein interaction database and analysis system More...IntActi | Q13501, 152 interactors |
Molecular INTeraction database More...MINTi | Q13501 |
STRING: functional protein association networks More...STRINGi | 9606.ENSP00000374455 |
<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsHide details| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Structure’ section is used to indicate the positions of experimentally determined beta strands within the protein sequence.<p><a href='/help/strand' target='_top'>More...</a></p>Beta strandi | 5 – 10 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 6 | |
| Beta strandi | 19 – 24 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 6 | |
| <p>This subsection of the ‘Structure’ section is used to indicate the positions of experimentally determined helical regions within the protein sequence.<p><a href='/help/helix' target='_top'>More...</a></p>Helixi | 43 – 54 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 12 | |
| Beta strandi | 62 – 64 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 66 – 68 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 74 – 76 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Helixi | 80 – 88 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 9 | |
| Beta strandi | 92 – 101 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 10 | |
| <p>This subsection of the ‘Structure’ section is used to indicate the positions of experimentally determined hydrogen-bonded turns within the protein sequence. These elements correspond to the DSSP secondary structure code ‘T’.<p><a href='/help/turn' target='_top'>More...</a></p>Turni | 129 – 131 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 132 – 134 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 137 – 147 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 11 | |
| Helixi | 152 – 156 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Turni | 157 – 162 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 6 | |
| Beta strandi | 165 – 168 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Beta strandi | 388 – 390 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Helixi | 392 – 402 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 11 | |
| Turni | 403 – 405 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 409 – 411 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Helixi | 412 – 419 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 8 | |
| Turni | 420 – 422 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Helixi | 424 – 431 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 8 | |
| Beta strandi | 432 – 434 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 |
3D structure databases
| Select the link destinations: Protein Data Bank Europe More...PDBeiProtein Data Bank RCSB More...RCSB PDBiProtein Data Bank Japan More...PDBjiLinks Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 1Q02 | NMR | - | A | 387-436 | [»] | |
| 2JY7 | NMR | - | A | 387-436 | [»] | |
| 2JY8 | NMR | - | A | 387-436 | [»] | |
| 2K0B | NMR | - | X | 387-436 | [»] | |
| 2KNV | NMR | - | A/B | 387-436 | [»] | |
| 4MJS | X-ray | 2.50 | B/D/F/H/J/L/N/P/R/T/V/X | 3-102 | [»] | |
| 4UF8 | electron microscopy | 10.90 | A/B/C/I | 3-102 | [»] | |
| 4UF9 | electron microscopy | 10.30 | A/B/D | 1-122 | [»] | |
| 5YP7 | X-ray | 1.42 | A/D | 126-180 | [»] | |
| 5YP8 | X-ray | 1.45 | A/B | 126-180 | [»] | |
| 5YPA | X-ray | 2.50 | A/B | 126-180 | [»] | |
| 5YPB | X-ray | 2.90 | A/B/C/D | 126-180 | [»] | |
| 5YPC | X-ray | 1.96 | A/B/C/D | 126-180 | [»] | |
| 5YPE | X-ray | 2.85 | A/B/C/D | 126-180 | [»] | |
| 5YPF | X-ray | 2.95 | A/B/C/D | 126-180 | [»] | |
| 5YPG | X-ray | 2.20 | A/B | 126-180 | [»] | |
| 5YPH | X-ray | 1.63 | A/B | 126-180 | [»] | |
| 6MJ7 | X-ray | 1.41 | A | 120-171 | [»] | |
Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase More...ProteinModelPortali | Q13501 | |||||
SWISS-MODEL Repository - a database of annotated 3D protein structure models More...SMRi | Q13501 | |||||
Database of comparative protein structure models More...ModBasei | Search... | |||||
MobiDB: a database of protein disorder and mobility annotations More...MobiDBi | Search... | |||||
Miscellaneous databases
Relative evolutionary importance of amino acids within a protein sequence More...EvolutionaryTracei | Q13501 |
<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini | 3 – 102 | PB1PROSITE-ProRule annotation Manual assertion according to rulesi Add BLAST | 100 | |
| Domaini | 389 – 434 | UBAPROSITE-ProRule annotation Manual assertion according to rulesi Add BLAST | 46 |
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni | 2 – 50 | Interaction with LCKAdd BLAST | 49 | |
| Regioni | 43 – 107 | Interaction with PRKCZ and dimerizationBy similarityAdd BLAST | 65 | |
| Regioni | 50 – 80 | Interaction with PAWR1 Publication Manual assertion based on experiment ini
| 31 | |
| Regioni | 122 – 224 | Interaction with GABRR3By similarityAdd BLAST | 103 | |
| Regioni | 170 – 220 | LIM protein-binding (LB)Add BLAST | 51 | |
| Regioni | 269 – 440 | Interaction with NTRK1By similarityAdd BLAST | 172 | |
| Regioni | 321 – 342 | MAP1LC3B-bindingAdd BLAST | 22 |
Motif
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi | 228 – 233 | TRAF6-binding | 6 | |
| Motifi | 336 – 341 | LIR | 6 |
Compositional bias
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi | 272 – 294 | Ser-richAdd BLAST | 23 |
<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini
The UBA domain binds specifically 'Lys-63'-linked polyubiquitin chains of polyubiquitinated substrates. Mediates the interaction with TRIM55. Both the UBA and PB1 domains are necessary and sufficient for the localization into the ubiquitin-containing inclusion bodies.2 Publications
Manual assertion based on experiment ini
- Ref.24"Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation."
Seibenhener M.L., Babu J.R., Geetha T., Wong H.C., Krishna N.R., Wooten M.W.
Mol. Cell. Biol. 24:8055-8068(2004) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH TRAF6; PSMC2 AND PSMD4, DOMAIN, MUTAGENESIS OF LEU-398; PHE-406; LEU-413; LEU-417 AND ILE-431, FUNCTION. - Ref.73"Structure of the ubiquitin-associated domain of p62 (SQSTM1) and implications for mutations that cause Paget's disease of bone."
Ciani B., Layfield R., Cavey J.R., Sheppard P.W., Searle M.S.
J. Biol. Chem. 278:37409-37412(2003) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY NMR OF 387-436, CHARACTERIZATION OF VARIANT LEU-392, DOMAIN.
The PB1 domain mediates homooligomerization and interactions with FHOD3, MAP2K5, NBR1, PRKCI, PRKCZ and WDR81. Both the PB1 and UBA domains are necessary and sufficient for the localization into the ubiquitin-containing inclusion bodies.4 Publications
Manual assertion based on experiment ini
- Ref.20"Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins."
Lamark T., Perander M., Outzen H., Kristiansen K., Oevervatn A., Michaelsen E., Bjoerkoey G., Johansen T.
J. Biol. Chem. 278:34568-34581(2003) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH PRKCI; PRKCZ; MAP2K5 AND NBR1, DOMAIN, MUTAGENESIS OF LYS-7; LYS-13; 21-ARG-ARG-22; TYR-67; ASP-69; ASP-71; ASP-73; ASP-80 AND GLU-82, DIMERIZATION. - Ref.21"PB1 domain-mediated heterodimerization in NADPH oxidase and signaling complexes of atypical protein kinase C with Par6 and p62."
Wilson M.I., Gill D.J., Perisic O., Quinn M.T., Williams R.L.
Mol. Cell 12:39-50(2003) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH PRKCZ, DOMAIN, OLIGOMERIZATION, MUTAGENESIS OF LYS-7; ASP-69 AND ASP-73. - Ref.31"The kinase domain of titin controls muscle gene expression and protein turnover."
Lange S., Xiang F., Yakovenko A., Vihola A., Hackman P., Rostkova E., Kristensen J., Brandmeier B., Franzen G., Hedberg B., Gunnarsson L.G., Hughes S.M., Marchand S., Sejersen T., Richard I., Edstroem L., Ehler E., Udd B., Gautel M.
Science 308:1599-1603(2005) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH NBR1 AND TRIM55, PHOSPHORYLATION, DOMAINS, FUNCTION. - Ref.71"The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy."
Liu X., Li Y., Wang X., Xing R., Liu K., Gan Q., Tang C., Gao Z., Jian Y., Luo S., Guo W., Yang C.
J. Cell Biol. 216:1301-1320(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH WDR81, DOMAIN.
The ZZ-type zinc finger mediates the interaction with RIPK1.1 Publication
Manual assertion based on experiment ini
- Ref.14"The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway."
Sanz L., Diaz-Meco M.T., Nakano H., Moscat J.
EMBO J. 19:1576-1586(2000) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH TRAF6 AND RIPK1, DOMAIN, FUNCTION.
The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins.1 Publication
Manual assertion based on experiment ini
- Ref.57"The LIR motif - crucial for selective autophagy."
Birgisdottir A.B., Lamark T., Johansen T.
J. Cell Sci. 126:3237-3247(2013) [PubMed] [Europe PMC] [Abstract]Cited for: LIR MOTIF.
Zinc finger
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Zinc fingeri | 122 – 167 | ZZ-typePROSITE-ProRule annotation Manual assertion according to rulesi Add BLAST | 46 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
evolutionary genealogy of genes: Non-supervised Orthologous Groups More...eggNOGi | KOG4582 Eukaryota ENOG410XYAV LUCA |
Ensembl GeneTree More...GeneTreei | ENSGT00390000002781 |
The HOVERGEN Database of Homologous Vertebrate Genes More...HOVERGENi | HBG052750 |
InParanoid: Eukaryotic Ortholog Groups More...InParanoidi | Q13501 |
KEGG Orthology (KO) More...KOi | K14381 |
Identification of Orthologs from Complete Genome Data More...OMAi | KNCDIGA |
Database of Orthologous Groups More...OrthoDBi | 1275680at2759 |
Database for complete collections of gene phylogenies More...PhylomeDBi | Q13501 |
TreeFam database of animal gene trees More...TreeFami | TF328470 |
Family and domain databases
Conserved Domains Database More...CDDi | cd06402 PB1_p62, 1 hit cd14320 UBA_SQSTM, 1 hit |
Integrated resource of protein families, domains and functional sites More...InterProi | View protein in InterPro IPR000270 PB1_dom IPR034866 PB1_p62 IPR033741 SQSTM_UBA IPR015940 UBA IPR009060 UBA-like_sf IPR000433 Znf_ZZ |
Pfam protein domain database More...Pfami | View protein in Pfam PF00564 PB1, 1 hit PF16577 UBA_5, 1 hit PF00569 ZZ, 1 hit |
Simple Modular Architecture Research Tool; a protein domain database More...SMARTi | View protein in SMART SM00666 PB1, 1 hit SM00165 UBA, 1 hit SM00291 ZnF_ZZ, 1 hit |
Superfamily database of structural and functional annotation More...SUPFAMi | SSF46934 SSF46934, 1 hit |
PROSITE; a protein domain and family database More...PROSITEi | View protein in PROSITE PS51745 PB1, 1 hit PS50030 UBA, 1 hit PS01357 ZF_ZZ_1, 1 hit PS50135 ZF_ZZ_2, 1 hit |
<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i
<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.
<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.
This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basketAdded to basketThis entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q13501-1) [UniParc]FASTAAdd to basketAdded to basket
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
« Hide
Show »10 20 30 40 50
MASLTVKAYL LGKEDAAREI RRFSFCCSPE PEAEAEAAAG PGPCERLLSR
60 70 80 90 100
VAALFPALRP GGFQAHYRDE DGDLVAFSSD EELTMAMSYV KDDIFRIYIK
110 120 130 140 150
EKKECRRDHR PPCAQEAPRN MVHPNVICDG CNGPVVGTRY KCSVCPDYDL
160 170 180 190 200
CSVCEGKGLH RGHTKLAFPS PFGHLSEGFS HSRWLRKVKH GHFGWPGWEM
210 220 230 240 250
GPPGNWSPRP PRAGEARPGP TAESASGPSE DPSVNFLKNV GESVAAALSP
260 270 280 290 300
LGIEVDIDVE HGGKRSRLTP VSPESSSTEE KSSSQPSSCC SDPSKPGGNV
310 320 330 340 350
EGATQSLAEQ MRKIALESEG RPEEQMESDN CSGGDDDWTH LSSKEVDPST
360 370 380 390 400
GELQSLQMPE SEGPSSLDPS QEGPTGLKEA ALYPHLPPEA DPRLIESLSQ
410 420 430 440
MLSMGFSDEG GWLTRLLQTK NYDIGAALDT IQYSKHPPPL
Length:440
Mass (Da):47,687
Last modified:November 1, 1996 - v1
<p>The checksum is a form of redundancy check that is calculated
from the sequence. It is useful for tracking sequence updates.</p>
<p>It should be noted that while, in theory, two different sequences could
have the same checksum value, the likelihood that this would happen
is extremely low.</p>
<p>However UniProtKB may contain entries with identical sequences in case
of multiple genes (paralogs).</p>
<p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64)
using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1.
The algorithm is described in the ISO 3309 standard.
</p>
<p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br />
<strong>Cyclic redundancy and other checksums</strong><br />
<a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p>
Checksum:i462D94C171F337CD
Isoform 2 (identifier: Q13501-2) [UniParc]FASTAAdd to basketAdded to basket
The sequence of this isoform differs from the canonical sequence as follows:
1-84: Missing.
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MAMSYVKDDI FRIYIKEKKE CRRDHRPPCA QEAPRNMVHP NVICDGCNGP
60 70 80 90 100
VVGTRYKCSV CPDYDLCSVC EGKGLHRGHT KLAFPSPFGH LSEGFSHSRW
110 120 130 140 150
LRKVKHGHFG WPGWEMGPPG NWSPRPPRAG EARPGPTAES ASGPSEDPSV
160 170 180 190 200
NFLKNVGESV AAALSPLGIE VDIDVEHGGK RSRLTPVSPE SSSTEEKSSS
210 220 230 240 250
QPSSCCSDPS KPGGNVEGAT QSLAEQMRKI ALESEGRPEE QMESDNCSGG
260 270 280 290 300
DDDWTHLSSK EVDPSTGELQ SLQMPESEGP SSLDPSQEGP TGLKEAALYP
310 320 330 340 350
HLPPEADPRL IESLSQMLSM GFSDEGGWLT RLLQTKNYDI GAALDTIQYS
KHPPPL
<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi
There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket| Entry | Entry name | Protein names | Gene names | Length | Annotation | ||
|---|---|---|---|---|---|---|---|
| E7EMC7 | E7EMC7_HUMAN | Sequestosome-1 Sequestosome-1 | SQSTM1 | 378 | Annotation score: Annotation score:1 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| C9JRJ8 | C9JRJ8_HUMAN | Sequestosome-1 Sequestosome-1 | SQSTM1 | 140 | Annotation score: Annotation score:1 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| E9PFW8 | E9PFW8_HUMAN | Sequestosome-1 Sequestosome-1 | SQSTM1 | 167 | Annotation score: Annotation score:1 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| E3W990 | E3W990_HUMAN | Sequestosome-1 Sequestosome-1 | SQSTM1 | 190 | Annotation score: Annotation score:1 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| D6RBF1 | D6RBF1_HUMAN | Sequestosome-1 Sequestosome-1 | SQSTM1 | 69 | Annotation score: Annotation score:1 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| C9J6J8 | C9J6J8_HUMAN | Sequestosome-1 Sequestosome-1 | SQSTM1 | 73 | Annotation score: Annotation score:1 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti | 321 | R → A in AAA93299 (PubMed:8551575).Curated | 1 |