Tbio SQSTM1 Sequestosome-1

Protein Summary

Description

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). 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]

Uniprot Accession IDs

• Q13501
• A6NFN7
• B2R661
• B3KUW5
• Q13446
• Q9BUV7
• Q9BVS6
• Q9UEU1

Gene Name

• SQSTM1

Ensembl ID

• ENST00000360718
• ENSP00000353944
• ENSG00000161011
• ENST00000389805
• ENSP00000374455

Symbol

• ORCA
• OSIL
• p60
• p62
• A170
• DMRV
• OSIL
• PDB3
• ZIP3
• p62B
• NADGP
• FTDALS3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
hub protein	1
interacting protein	1
biological process	0.96
drug perturbation	0.96
transcription factor perturbation	0.96

Related Tools

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1093.21   (req: < 5)

Gene RIFs: 324   (req: <= 3)

Antibodies: 1081   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1093.21   (req: >= 5)

Gene RIFs: 324   (req: > 3)

Antibodies: 1081   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 45

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

GWAS Traits (4)

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 4 of 4

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
neutrophil count	EFO_0004833	1	1	1		71.3
monocyte percentage of leukocytes	EFO_0007989	1	1	1		50.6
lymphocyte count	EFO_0004587	1	1	1		43.5
neutrophil percentage of leukocytes	EFO_0007990	1	1	1		9.5

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 4 of 4

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
neutrophil count	EFO_0004833	1		71.3
monocyte percentage of leukocytes	EFO_0007989	1		50.6
lymphocyte count	EFO_0004587	1		43.5
neutrophil percentage of leukocytes	EFO_0007990	1		9.5

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Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	sequestosome 1	VGNC:4180	462333
Macaque	sequestosome 1		705481
Mouse	sequestosome 1	MGI:107931	18412
Rat	sequestosome 1	RGD:69287	113894
Dog	sequestosome 1	VGNC:46787	481459

Species	Name	OMA	EggNOG	Inparanoid
Chimp	sequestosome 1
Macaque	sequestosome 1
Mouse	sequestosome 1
Rat	sequestosome 1
Dog	sequestosome 1

Protein Structure (17 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-Q13501-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 17

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (122)

Reactome (18)

KEGG (6)

PathwayCommons (6)

WikiPathways (92)

Autophagy (R-HSA-9612973)

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Find Similar Targets

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Autophagy	109 targets	R-HSA-9612973
Reactome	Cell death signalling via NRAGE, NRIF and NADE	76 targets	R-HSA-204998
Reactome	Cellular responses to external stimuli	487 targets	R-HSA-8953897
Reactome	Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Reactome	Death Receptor Signalling	141 targets	R-HSA-73887

Name	Explore in Pharos	Explore in Source
Autophagy	109 targets	R-HSA-9612973
Cell death signalling via NRAGE, NRIF and NADE	76 targets	R-HSA-204998
Cellular responses to external stimuli	487 targets	R-HSA-8953897
Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Death Receptor Signalling	141 targets	R-HSA-73887

Gene Ontology Terms (64)

Functions (13)

Components (19)

Processes (32)

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Items per page:

10

1 – 10 of 13

GO Term	Evidence	Assigned by
K63-linked polyubiquitin modification-dependent protein binding	Inferred from Direct Assay (IDA)	UniProtKB
protein kinase binding	Inferred from Direct Assay (IDA)	UniProtKB
SH2 domain binding	Inferred from Direct Assay (IDA)	UniProtKB
ubiquitin binding	Inferred from Direct Assay (IDA)	UniProtKB
ubiquitin protein ligase binding	Inferred from Direct Assay (IDA)	UniProtKB
enzyme binding	Inferred from Physical Interaction (IPI)	UniProtKB
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
protein kinase C binding	Inferred from Physical Interaction (IPI)	UniProtKB
ionotropic glutamate receptor binding	Inferred from Sequence or structural Similarity (ISS)	ARUK-UCL
receptor tyrosine kinase binding	Traceable Author Statement (TAS)	ProtInc

Protein-Protein Interactions (336)

Explore Interacting Targets

1 – 10 of 336

• See Interactions on String-DB

RETN

Tbio

Novelty: 0.00062517

p_int: 0.997093079

p_ni: 0.002906921

Score: 0.187

Data Source: BioPlex,STRINGDB

EDDM3B

Tdark

Novelty: 0.12874735

p_int: 0.98461159

p_ni: 0.01538841

Data Source: BioPlex

KERA

Tbio

Novelty: 0.00789599

p_int: 0.979900907

p_ni: 0.020099093

Score: 0.202

Data Source: BioPlex,STRINGDB

PRKCZ

Tchem

Family: Kinase

Novelty: 0.00201366

p_int: 0.971148548

p_ni: 0.028851452

Score: 0.955

Data Source: BioPlex,STRINGDB

INSL5

Tbio

Novelty: 0.04351334

p_int: 0.971088926

p_ni: 0.028911074

Data Source: BioPlex

TMX1

Tbio

Novelty: 0.03444237

p_int: 0.96615906

p_ni: 0.03384094

Data Source: BioPlex

VWCE

Tbio

Novelty: 0.09328341

p_int: 0.963341853

p_ni: 0.036658147

Score: 0.243

Data Source: BioPlex,STRINGDB

CD96

Tbio

Novelty: 0.02087722

p_int: 0.952239612

p_ni: 0.047760388

Score: 0.187

Data Source: BioPlex,STRINGDB

IL17F

Tbio

Novelty: 0.00223549

p_int: 0.94672289

p_ni: 0.05327711

Data Source: BioPlex

IL7R

Tbio

Novelty: 0.00107223

p_int: 0.929257106

p_ni: 0.070742894

Data Source: BioPlex

Publication Statistics

PubMed Score  1093.21

PubMed score by year

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PubTator Score  598.55

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Acetylation
Alternative splicing
Amyotrophic lateral sclerosis
Apoptosis
Autophagy
Complete proteome
Cytoplasm
Cytoplasmic vesicle
Differentiation

GWAS Trait Find Similar Targets

lymphocyte count
monocyte percentage of leukocytes
neutrophil count
neutrophil percentage of leukocytes

MGI Phenotype Find Similar Targets

adipose tissue phenotype
behavior/neurological phenotype
cellular phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype
liver/biliary system phenotype
mortality/aging