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    SQSTM1 sequestosome 1 [ Homo sapiens (human) ]

    Gene ID: 8878, updated on 28-Oct-2024

    Summary

    Official Symbol
    SQSTM1provided by HGNC
    Official Full Name
    sequestosome 1provided by HGNC
    Primary source
    HGNC:HGNC:11280
    See related
    Ensembl:ENSG00000161011 MIM:601530; AllianceGenome:HGNC:11280
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    p60; p62; A170; DMRV; OSIL; PDB3; ZIP3; p62B; EBIAP; NADGP; FTDALS3
    Summary
    This gene encodes a multifunctional protein that binds ubiquitin and regulates activation of the nuclear factor kappa-B (NF-kB) signaling pathway. The protein functions as a scaffolding/adaptor protein in concert with TNF receptor-associated factor 6 to mediate activation of NF-kB in response to upstream signals. Alternatively spliced transcript variants encoding either the same or different isoforms have been identified for this gene. Mutations in this gene result in sporadic and familial Paget disease of bone. [provided by RefSeq, Mar 2009]
    Expression
    Ubiquitous expression in thyroid (RPKM 57.3), gall bladder (RPKM 54.3) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See SQSTM1 in Genome Data Viewer
    Location:
    5q35.3
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (179806393..179838078)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (180361589..180393289)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (179233393..179265078)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16735 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:179222110-179222782 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16737 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:179223416-179223627 Neighboring gene leukotriene C4 synthase Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16739 Neighboring gene microRNA 1229 Neighboring gene alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase B Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:179233022-179233683 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16743 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16744 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:179238425-179239203 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16745 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16746 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr5:179245687-179246886 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:179247407-179248116 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16749 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16750 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:179250225-179250763 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:179250764-179251301 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:179254671-179255475 Neighboring gene Sharpr-MPRA regulatory region 15558 Neighboring gene MRN complex interacting protein Neighboring gene RN7SK pseudogene 150 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:179278643-179278802 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23765 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16751 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23766 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16752 Neighboring gene MRNIP divergent transcript

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    Treatment of macrophages (24-72 hours) with purified HIV-1 decreases SQSTM1 in a dose-dependent manner in the absence of cytotoxic effects (indicates induction and flux of autophagy)with observed increase is lost at day 7 post-infection onward PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 Env gp120 treatment of SH-SY5Y cells decreases SQSTM1 (p62) which indicates the progression of the autophagic process PubMed
    Nef nef HIV-1 Nef upregulates the expression of p62 protein in human mesenchymal stem cells PubMed
    Tat tat HIV-1 Tat downregulates sequestosome 1 (SQSTM1, p62) levels in a dose-dependent manner in neuronal cells PubMed
    tat The interaction of SQSTM1/p62 with HIV-1 Tat is required for Tat degradation by the autophagy pathway in an ubiquitin-independent manner PubMed
    Vif vif HIV-1 Vif is identified to have a physical interaction with sequestosome 1 (SQSTM1) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
    capsid gag HIV-1 CA colocalizes with MAP1LC3B2 and MAP1LC3B2/SQSTM1 as demonstrated via fluorescence microscopy PubMed
    matrix gag HIV-1 p55/p17 (Gag-precursor) colocalizes with MAP1LC3B2 and MAP1LC3B2/SQSTM1 as demonstrated via fluorescence microscopy PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables K63-linked polyubiquitin modification-dependent protein binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables K63-linked polyubiquitin modification-dependent protein binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables SH2 domain binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables ionotropic glutamate receptor binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables molecular condensate scaffold activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables molecular sequestering activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase C binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables protein kinase C binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein sequestering activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein-containing complex binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein-macromolecule adaptor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables receptor tyrosine kinase binding TAS
    Traceable Author Statement
    more info
    PubMed 
    enables signaling receptor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables ubiquitin binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables ubiquitin binding TAS
    Traceable Author Statement
    more info
     
    enables ubiquitin protein ligase binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables ubiquitin-modified protein reader activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    involved_in aggrephagy IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in aggrephagy IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in aggrephagy IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    involved_in apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in autophagy IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in autophagy IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in autophagy TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in autophagy of mitochondrion NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in brown fat cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to stress IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in endosomal transport TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in endosome organization IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in endosome organization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in energy homeostasis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in immune system process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in intracellular signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in macroautophagy IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in macroautophagy ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in mitophagy IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in mitophagy IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in negative regulation of ferroptosis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of protein ubiquitination IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of toll-like receptor 4 signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of transcription by RNA polymerase II IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in non-membrane-bounded organelle assembly IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in pexophagy IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of apoptotic process TAS
    Traceable Author Statement
    more info
     
    involved_in positive regulation of autophagy IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of long-term synaptic potentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of protein localization to plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of transcription by RNA polymerase II TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in protein catabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein import into nucleus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in protein localization TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in protein localization to perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein targeting to vacuole involved in autophagy IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of Ras protein signal transduction NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in regulation of canonical NF-kappaB signal transduction IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of mitochondrion organization NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in regulation of protein complex stability IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in response to ischemia IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to mitochondrial depolarisation IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in temperature homeostasis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in transcription by RNA polymerase II IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in ubiquitin-dependent protein catabolic process TAS
    Traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in Lewy body IEA
    Inferred from Electronic Annotation
    more info
     
    located_in P-body IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in PML body IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in aggresome IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    is_active_in amphisome IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in amphisome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in autolysosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in autophagosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in autophagosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in cytoplasm IC
    Inferred by Curator
    more info
    PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
     
    located_in cytosol TAS
    Traceable Author Statement
    more info
    PubMed 
    located_in endoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
     
    located_in extracellular exosome HDA PubMed 
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
     
    located_in inclusion body IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
     
    is_active_in intracellular non-membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in late endosome IEA
    Inferred from Electronic Annotation
    more info
     
    located_in mitochondrion IEA
    Inferred from Electronic Annotation
    more info
     
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
     
    located_in phagophore assembly site IEA
    Inferred from Electronic Annotation
    more info
     
    located_in sarcomere IEA
    Inferred from Electronic Annotation
    more info
     
    located_in sperm midpiece IEA
    Inferred from Electronic Annotation
    more info
     

    General protein information

    Preferred Names
    sequestosome-1
    Names
    EBI3-associated protein of 60 kDa
    EBI3-associated protein p60
    autophagy receptor p62
    oxidative stress induced like
    phosphotyrosine independent ligand for the Lck SH2 domain p62
    phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa
    ubiquitin-binding protein p62

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011342.1 RefSeqGene

      Range
      19518..36691
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001142298.2 → NP_001135770.1  sequestosome-1 isoform 2

      See identical proteins and their annotated locations for NP_001135770.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation from an in-frame downstream start codon compared to variant 1. This results in an isoform (2) with a shorter N-terminus compared to isoform 1. Variants 2 and 3 encode the same isoform.
      Source sequence(s)
      BC000951, BC017222, BI549805, BU625974
      Consensus CDS
      CCDS47355.1
      UniProtKB/Swiss-Prot
      Q13501
      Conserved Domains (3) summary
      cd02340
      Location:42 → 84
      ZZ_NBR1_like; Zinc finger, ZZ type. Zinc finger present in Drosophila ref(2)P, NBR1, Human sequestosome 1 and related proteins. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding. Drosophila ref(2)P appears ...
      pfam16577
      Location:295 → 356
      UBA_5; UBA domain
      cl02720
      Location:1 → 18
      PB1; The PB1 domain is a modular domain mediating specific protein-protein interactions which play a role in many critical cell processes, such as osteoclastogenesis, angiogenesis, early cardiovascular development, and cell polarity. A canonical PB1-PB1 ...
    2. NM_001142299.2 → NP_001135771.1  sequestosome-1 isoform 2

      See identical proteins and their annotated locations for NP_001135771.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation from an in-frame downstream start codon compared to variant 1. This results in an isoform (2) with a shorter N-terminus compared to isoform 1. Variants 2 and 3 differ in the 5' UTR, but encode the same isoform.
      Source sequence(s)
      BC000951, BC017222, BU625974, DA541885
      Consensus CDS
      CCDS47355.1
      UniProtKB/Swiss-Prot
      Q13501
      Related
      ENSP00000353944.5, ENST00000360718.5
      Conserved Domains (3) summary
      cd02340
      Location:42 → 84
      ZZ_NBR1_like; Zinc finger, ZZ type. Zinc finger present in Drosophila ref(2)P, NBR1, Human sequestosome 1 and related proteins. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding. Drosophila ref(2)P appears ...
      pfam16577
      Location:295 → 356
      UBA_5; UBA domain
      cl02720
      Location:1 → 18
      PB1; The PB1 domain is a modular domain mediating specific protein-protein interactions which play a role in many critical cell processes, such as osteoclastogenesis, angiogenesis, early cardiovascular development, and cell polarity. A canonical PB1-PB1 ...
    3. NM_003900.5 → NP_003891.1  sequestosome-1 isoform 1

      See identical proteins and their annotated locations for NP_003891.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the predominant transcript, and encodes the longer isoform (1).
      Source sequence(s)
      AI333228, BC000951, BC017222, DC398116
      Consensus CDS
      CCDS34317.1
      UniProtKB/Swiss-Prot
      A6NFN7, B2R661, B3KUW5, Q13446, Q13501, Q9BUV7, Q9BVS6, Q9UEU1
      Related
      ENSP00000374455.4, ENST00000389805.9
      Conserved Domains (3) summary
      cd06402
      Location:4 → 102
      PB1_p62; The PB1 domain is an essential part of p62 scaffold protein (alias sequestosome 1,SQSTM) involved in cell signaling, receptor internalization, and protein turnover. The PB1 domain is a modular domain mediating specific protein-protein interaction which ...
      cd02340
      Location:126 → 168
      ZZ_NBR1_like; Zinc finger, ZZ type. Zinc finger present in Drosophila ref(2)P, NBR1, Human sequestosome 1 and related proteins. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding. Drosophila ref(2)P appears ...
      pfam16577
      Location:379 → 440
      UBA_5; UBA domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      179806393..179838078
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107298.1 Reference GRCh38.p14 PATCHES

      Range
      571962..603638
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      180361589..180393289
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)