SQSTM1 sequestosome 1 [Homo sapiens (human)] - Gene

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; 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: mouse all
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Genomic context

Location:: 5q35.3

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (179806393..179838078)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (180361589..180393289)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (179233393..179265078)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

circRNA_SLC8A1 promotes the survival of mycobacterium tuberculosis in macrophages by upregulating expression of autophagy-related protein SQSTM1/p62 to activate the NF-kappaB pathway.
Title: circRNA_SLC8A1 promotes the survival of mycobacterium tuberculosis in macrophages by upregulating expression of autophagy-related protein SQSTM1/p62 to activate the NF-κB pathway.
Endothelium-specific deletion of p62 causes organ fibrosis and cardiac dysfunction.
Title: Endothelium-specific deletion of p62 causes organ fibrosis and cardiac dysfunction.
Nuclear-cytoplasmic translocation of SQSTM1/p62 protein enhances ESCC cell migration and invasion by stabilizing EPLIN expression.
Title: Nuclear-cytoplasmic translocation of SQSTM1/p62 protein enhances ESCC cell migration and invasion by stabilizing EPLIN expression.
SQSTM1/p62 inhibition impairs pro-survival signaling in hypoxic human dendritic cells.
Title: SQSTM1/p62 inhibition impairs pro-survival signaling in hypoxic human dendritic cells.
Distal myopathy due to digenic inheritance of TIA1 and SQSTM1 variants in two unrelated Spanish patients.
Title: Distal myopathy due to digenic inheritance of TIA1 and SQSTM1 variants in two unrelated Spanish patients.
TRIM11 attenuates Treg cell differentiation by p62-selective autophagic degradation of AIM2.
Title: TRIM11 attenuates Treg cell differentiation by p62-selective autophagic degradation of AIM2.
Cancer-associated fibroblasts-derived CXCL12 enhances immune escape of bladder cancer through inhibiting P62-mediated autophagic degradation of PDL1.
Title: Cancer-associated fibroblasts-derived CXCL12 enhances immune escape of bladder cancer through inhibiting P62-mediated autophagic degradation of PDL1.
The role of p62 in cell death and survival of 5-fluorouracil and oxaliplatin-resistant colorectal cancer cells.
Title: The role of p62 in cell death and survival of 5-fluorouracil and oxaliplatin-resistant colorectal cancer cells.
USP13 deubiquitinates p62/SQSTM1 to induce autophagy and Nrf2 release for activating antioxidant response genes.
Title: USP13 deubiquitinates p62/SQSTM1 to induce autophagy and Nrf2 release for activating antioxidant response genes.
The selective autophagy adaptor p62/SQSTM1 forms phase condensates regulated by HSP27 that facilitate the clearance of damaged lysosomes via lysophagy.
Title: The selective autophagy adaptor p62/SQSTM1 forms phase condensates regulated by HSP27 that facilitate the clearance of damaged lysosomes via lysophagy.

Submit: New GeneRIF Correction See all GeneRIFs (485)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 MedGen: C4225326 OMIM: 616437 GeneReviews: Amyotrophic Lateral Sclerosis Overview	Compare labs
Myopathy, distal, with rimmed vacuoles MedGen: C5399975 OMIM: 617158 GeneReviews: Not available	Compare labs
Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset MedGen: C4310693 OMIM: 617145 GeneReviews: Not available	Compare labs
Paget disease of bone 3 MedGen: C4085252 OMIM: 167250 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-182 (e-PCR)
- UniSTS:90665

SHGC-33017 (e-PCR)
- UniSTS:55337

D5S2223E (e-PCR)
- UniSTS:154429

D11S4452 (e-PCR)
- UniSTS:154758

D5S2306E (e-PCR)
- UniSTS:154514

TMSB4X (e-PCR)
- UniSTS:506515

A008T21 (e-PCR)
- UniSTS:49555

RH70719 (e-PCR)
- UniSTS:27561

RH91868 (e-PCR)
- UniSTS:84659

L18441 (e-PCR)
- UniSTS:71348

RH18060 (e-PCR)
- UniSTS:14267

MARC_4921-4922:991938931:1 (e-PCR)
- UniSTS:231122

STS-Z40707 (e-PCR)
- UniSTS:72414

A002O27 (e-PCR)
- UniSTS:21750

RH98565 (e-PCR)
- UniSTS:89592

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 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 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 protein phosphorylation	IEA Inferred from Electronic Annotation 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 more info	PubMed
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

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Preferred Names: sequestosome-1

Names: EBI3-associated protein of 60 kDa; EBI3-associated protein p60; EBIAP; 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)

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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

NG_011342.1 RefSeqGene

Range

19518..36691

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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 ...
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 ...
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