Sqstm1 sequestosome 1 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Sqstm1provided by RGD
Official Full Name: sequestosome 1provided by RGD
Primary source: RGD:69287
See related: EnsemblRapid:ENSRNOG00000003147 AllianceGenome:RGD:69287
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Osi; ZIP; ZIP3
Summary: Enables identical protein binding activity and protein kinase C binding activity. Involved in positive regulation of protein phosphorylation and response to ischemia. Located in Lewy body. Is active in glutamatergic synapse. Biomarker of glaucoma and hypertension. Human ortholog(s) of this gene implicated in Paget's disease of bone; Paget's disease of bone 3; distal myopathy with rimmed vacuoles; frontotemporal dementia and/or amyotrophic lateral sclerosis 3; and neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset. Orthologous to human SQSTM1 (sequestosome 1). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Biased expression in Liver (RPKM 1406.7), Muscle (RPKM 1246.9) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 10q22

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	10	NC_086028.1 (35026598..35037750, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	10	NC_051345.1 (34525517..34536670, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	10	NC_005109.4 (35704728..35716316, complement)

Chromosome 10 - NC_086028.1 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: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Activation of the p62-Keap1-Nrf2 pathway improves pulmonary arterial hypertension in MCT-induced rats by inhibiting autophagy.
Title: Activation of the p62-Keap1-Nrf2 pathway improves pulmonary arterial hypertension in MCT-induced rats by inhibiting autophagy.
The Relationship of p62 Gene Expression with Integrity of Mitochondrial DNA and the Level of Lipid Peroxidation Products in Skeletal Muscles of Rats of Different Ages Exposed to Different Feeding Protocols.
Title: The Relationship of p62 Gene Expression with Integrity of Mitochondrial DNA and the Level of Lipid Peroxidation Products in Skeletal Muscles of Rats of Different Ages Exposed to Different Feeding Protocols.
MiR-361-5p promotes oxygen-glucose deprivation/re-oxygenation induced neuronal injury by negatively regulating SQSTM1 in vitro.
Title: MiR-361-5p promotes oxygen-glucose deprivation/re-oxygenation induced neuronal injury by negatively regulating SQSTM1 in vitro.
Graphene oxide induces p62/SQSTM-dependent apoptosis through the impairment of autophagic flux and lysosomal dysfunction in PC12 cells.
Title: Graphene oxide induces p62/SQSTM-dependent apoptosis through the impairment of autophagic flux and lysosomal dysfunction in PC12 cells.
Data suggest that neuroprotection via ghrelin involves up-regulation of Bcl-2 (B cell lymphoma 2 associated oncogene) and p-62/Sqstm1 (ubiquitin-binding protein p62) plus down-regulation of LC3-II (microtubule-associated protein 1 light chain 3) and Beclin-1. Studies were conducted in adult hippocampal neural stem cells in primary culture.
Title: Ghrelin protects adult rat hippocampal neural stem cells from excessive autophagy during oxygen-glucose deprivation.
Quantifying autophagy using novel LC3B and p62 TR-FRET assays.
Title: Quantifying autophagy using novel LC3B and p62 TR-FRET assays.
Data suggest that phosphorylation of Sqstm1 by AMP-activated protein kinase (AMPK) and translocation of Sqstm1 to mitochondria drives autophagic cell death in adult hippocampal neural stem cells; activation of AMPK promotes autophagic cell death; inhibition of AMPK (by enzyme inhibitor or RNA interference) suppresses autophagic cell death. (Sqstm1 = sequestosome 1)
Title: Phosphorylation of p62 by AMP-activated protein kinase mediates autophagic cell death in adult hippocampal neural stem cells.
p62 overexpression resulted in a progressive and robust pathology model with neuronal inclusions and neurodegeneration.
Title: p62 Pathology Model in the Rat Substantia Nigra with Filamentous Inclusions and Progressive Neurodegeneration.
High glucose upregulates autophagy but accumulates p62/SQTSM1 cargo due to lysosomal dysfunction, leading to massive VEGF release and cell death of rMCs. Lysosomal impairment and autophagic dysfunction are early events present in the pathogenesis of diabetic retinopathy (DR).
Title: Defective Autophagy in Diabetic Retinopathy.
Parkin protects PC12 cells against 6-hydroxydopamine - induced apoptosis via ubiquitinating and stabilizing scaffold protein p62, and repressing ERK1/2 activation.
Title: Parkin represses 6-hydroxydopamine-induced apoptosis via stabilizing scaffold protein p62 in PC12 cells.

Submit: New GeneRIF Correction See all GeneRIFs (19)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AI851514 (e-PCR)
- UniSTS:185878

RH130114 (e-PCR)
- UniSTS:213402

RH143664 (e-PCR)
- UniSTS:232910

RH128379 (e-PCR)
- UniSTS:211687

Gene Ontology Provided by RGD

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	ISO Inferred from Sequence Orthology more info
enables K63-linked polyubiquitin modification-dependent protein binding	ISS Inferred from Sequence or Structural Similarity more info
enables SH2 domain binding	ISO Inferred from Sequence Orthology more info
enables SH2 domain binding	ISS Inferred from Sequence or Structural Similarity more info
enables enzyme binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	IPI Inferred from Physical Interaction more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables ionotropic glutamate receptor binding	ISO Inferred from Sequence Orthology more info
enables molecular condensate scaffold activity	ISO Inferred from Sequence Orthology more info
enables molecular sequestering activity	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info
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
enables protein kinase C binding	ISO Inferred from Sequence Orthology more info
enables protein kinase C binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein kinase binding	ISO Inferred from Sequence Orthology more info
enables protein sequestering activity	ISO Inferred from Sequence Orthology more info
enables protein sequestering activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein-containing complex binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-macromolecule adaptor activity	ISO Inferred from Sequence Orthology more info
enables protein-macromolecule adaptor activity	ISS Inferred from Sequence or Structural Similarity more info
enables signaling adaptor activity	ISO Inferred from Sequence Orthology more info
enables signaling receptor activity	ISO Inferred from Sequence Orthology more info
enables ubiquitin binding	ISO Inferred from Sequence Orthology more info
enables ubiquitin binding	ISS Inferred from Sequence or Structural Similarity more info
enables ubiquitin protein ligase binding	ISO Inferred from Sequence Orthology more info
enables ubiquitin-modified protein reader activity	ISO Inferred from Sequence Orthology more info
enables ubiquitin-modified protein reader activity	ISS Inferred from Sequence or Structural Similarity more info
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	ISO Inferred from Sequence Orthology more info
involved_in aggrephagy	ISS Inferred from Sequence or Structural Similarity more info
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in autophagy	ISO Inferred from Sequence Orthology more info
involved_in autophagy	ISS Inferred from Sequence or Structural Similarity more info
involved_in brown fat cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in cellular response to stress	ISO Inferred from Sequence Orthology more info
involved_in endosome organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in endosome organization	ISO Inferred from Sequence Orthology more info
involved_in endosome organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in energy homeostasis	ISO Inferred from Sequence Orthology more info
involved_in immune system process	IEA Inferred from Electronic Annotation more info
involved_in macroautophagy	ISO Inferred from Sequence Orthology more info
involved_in macroautophagy	ISS Inferred from Sequence or Structural Similarity more info
involved_in membraneless organelle assembly	ISO Inferred from Sequence Orthology more info
involved_in mitophagy	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitophagy	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of ferroptosis	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of ferroptosis	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of protein ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of protein ubiquitination	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of toll-like receptor 4 signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in pexophagy	ISO Inferred from Sequence Orthology more info
involved_in pexophagy	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of autophagy	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of long-term synaptic potentiation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein localization to plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein import into nucleus	ISO Inferred from Sequence Orthology more info
involved_in protein localization to perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info
involved_in protein localization to perinuclear region of cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in protein targeting to vacuole involved in autophagy	ISO Inferred from Sequence Orthology more info
involved_in protein targeting to vacuole involved in autophagy	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of canonical NF-kappaB signal transduction	ISO Inferred from Sequence Orthology more info
involved_in regulation of canonical NF-kappaB signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of protein complex stability	ISO Inferred from Sequence Orthology more info
involved_in response to ischemia	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to mitochondrial depolarisation	ISO Inferred from Sequence Orthology more info
involved_in temperature homeostasis	ISO Inferred from Sequence Orthology more info
acts_upstream_of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in Lewy body	IDA Inferred from Direct Assay more info	PubMed
located_in P-body	ISO Inferred from Sequence Orthology more info
located_in P-body	ISS Inferred from Sequence or Structural Similarity more info
located_in PML body	ISO Inferred from Sequence Orthology more info
is_active_in aggresome	IBA Inferred from Biological aspect of Ancestor more info
located_in aggresome	ISO Inferred from Sequence Orthology more info
is_active_in amphisome	IBA Inferred from Biological aspect of Ancestor more info
located_in amphisome	ISO Inferred from Sequence Orthology more info
located_in autolysosome	ISO Inferred from Sequence Orthology more info
located_in autophagosome	IEA Inferred from Electronic Annotation more info
is_active_in autophagosome	ISO Inferred from Sequence Orthology more info
located_in autophagosome	ISO Inferred from Sequence Orthology more info
located_in autophagosome	ISS Inferred from Sequence or Structural Similarity more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
is_active_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
located_in inclusion body	ISO Inferred from Sequence Orthology more info
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
is_active_in intracellular membraneless organelle	ISO Inferred from Sequence Orthology more info
is_active_in intracellular membraneless organelle	ISS Inferred from Sequence or Structural Similarity more info
located_in late endosome	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	ISO Inferred from Sequence Orthology more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in phagophore assembly site	ISO Inferred from Sequence Orthology more info
located_in sarcomere	IEA Inferred from Electronic Annotation more info
located_in sperm midpiece	ISO Inferred from Sequence Orthology more info
is_active_in synapse	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: sequestosome-1

Names: PKC-zeta-interacting protein; oxidative stress induced; protein kinase C-zeta-interacting protein; 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.

mRNA and Protein(s)

NM_001393884.1 → NP_001380813.1 sequestosome-1 isoform 3

Status: VALIDATED

Source sequence(s)

JAXUCZ010000010

UniProtKB/TrEMBL

A6HE00

Related

ENSRNOP00000004308.8, ENSRNOT00000004308.8

Conserved Domains (3) summary

cd06402
Location:4 → 100

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:123 → 163

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:351 → 412

UBA_5; UBA domain
NM_001393885.1 → NP_001380814.1 sequestosome-1 isoform 4

Status: VALIDATED

Source sequence(s)

JAXUCZ010000010

UniProtKB/TrEMBL

A6HE02

Conserved Domains (3) summary

cd06402
Location:4 → 100

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:123 → 163

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 ...

cl21463
Location:350 → 401

UBA_like_SF; UBA domain-like superfamily
NM_001393886.1 → NP_001380815.1 sequestosome-1 isoform 5

Status: VALIDATED

Source sequence(s)

JAXUCZ010000010

UniProtKB/TrEMBL

A6HE02

Conserved Domains (3) summary

cd06402
Location:4 → 100

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:123 → 163

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 ...

cl21463
Location:323 → 374

UBA_like_SF; UBA domain-like superfamily
NM_175843.5 → NP_787037.2 sequestosome-1 isoform 1

See identical proteins and their annotated locations for NP_787037.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

JAXUCZ010000010

UniProtKB/Swiss-Prot

O08623, Q8CH59

UniProtKB/TrEMBL

A6HE00

Related

ENSRNOP00000056021.4, ENSRNOT00000059255.7

Conserved Domains (3) summary

cd06402
Location:4 → 100

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:123 → 163

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:378 → 439

UBA_5; UBA domain
NM_181550.2 → NP_853528.2 sequestosome-1 isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks several exons and its transcription extends past a splice site that is used in variant 1. This results in a novel 3' coding region and 3' UTR, compared to variant 1. It encodes isoform 2 which is shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

JAXUCZ010000010

UniProtKB/TrEMBL

A6HE03

Conserved Domains (2) summary

cd06402
Location:4 → 100

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:123 → 163

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 ...