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SQSTM1 sequestosome 1 [ Homo sapiens (human) ]

Gene ID: 8878, updated on 19-Sep-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
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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)