TISIDB

Summary
Symbol	SQSTM1
Name	sequestosome 1
Aliases	p62B; A170; PDB3; OSIL; Paget disease of bone 3; oxidative stress induced like; FTDALS3; EBI3-associated pro ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cytoplasm, cytosol Late endosome. Lysosome. Cytoplasmic vesicle, autophagosome. Nucleus. Endoplasmic reticulum. Nucleus, PML body Cytoplasm, myofibril, sarcomere Note=In cardiac muscle, localizes to the sarcomeric band (By similarity). Commonly found in inclusion bodies containing polyubiquitinated protein aggregates. In neurodegenerative diseases, detected in Lewy bodies in Parkinson disease, neurofibrillary tangles in Alzheimer disease, and HTT aggregates in Huntington disease. In protein aggregate diseases of the liver, found in large amounts in Mallory bodies of alcoholic and nonalcoholic steatohepatitis, hyaline bodies in hepatocellular carcinoma, and in SERPINA1 aggregates. Enriched in Rosenthal fibers of pilocytic astrocytoma. In the cytoplasm, observed in both membrane-free ubiquitin-containing protein aggregates (sequestosomes) and membrane-surrounded autophagosomes. Colocalizes with TRIM13 in the perinuclear endoplasmic reticulum. Co-localizes with TRIM5 in cytoplasmic bodies. When nuclear export is blocked by treatment with leptomycin B, accumulates in PML bodies.
Domain	PF00564 PB1 domain PF16577 UBA domain PF00569 Zinc finger
Function	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).

> Gene Ontology [ TOP ]
Biological Process	GO:0000422 mitophagy GO:0000423 macromitophagy GO:0006914 autophagy GO:0007034 vacuolar transport GO:0007249 I-kappaB kinase/NF-kappaB signaling GO:0007265 Ras protein signal transduction GO:0010506 regulation of autophagy GO:0010508 positive regulation of autophagy GO:0010821 regulation of mitochondrion organization GO:0016197 endosomal transport GO:0016236 macroautophagy GO:0016239 positive regulation of macroautophagy GO:0016241 regulation of macroautophagy GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling GO:0043900 regulation of multi-organism process GO:0043901 negative regulation of multi-organism process GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism GO:0044110 growth involved in symbiotic interaction GO:0044116 growth of symbiont involved in interaction with host GO:0044117 growth of symbiont in host GO:0044126 regulation of growth of symbiont in host GO:0044130 negative regulation of growth of symbiont in host GO:0044144 modulation of growth of symbiont involved in interaction with host GO:0044146 negative regulation of growth of symbiont involved in interaction with host GO:0045926 negative regulation of growth GO:0046578 regulation of Ras protein signal transduction GO:0051056 regulation of small GTPase mediated signal transduction GO:0051259 protein oligomerization GO:0051291 protein heterooligomerization GO:0061635 regulation of protein complex stability GO:0061726 mitochondrion disassembly GO:0098779 mitophagy in response to mitochondrial depolarization GO:0098780 response to mitochondrial depolarisation GO:1903008 organelle disassembly
Molecular Function	GO:0004674 protein serine/threonine kinase activity GO:0005080 protein kinase C binding GO:0030971 receptor tyrosine kinase binding GO:0031593 polyubiquitin binding GO:0031625 ubiquitin protein ligase binding GO:0032182 ubiquitin-like protein binding GO:0042169 SH2 domain binding GO:0043130 ubiquitin binding GO:0044389 ubiquitin-like protein ligase binding GO:0070530 K63-linked polyubiquitin binding GO:1990782 protein tyrosine kinase binding
Cellular Component	GO:0000407 pre-autophagosomal structure GO:0000932 cytoplasmic mRNA processing body GO:0005767 secondary lysosome GO:0005770 late endosome GO:0005776 autophagosome GO:0005929 cilium GO:0016234 inclusion body GO:0016235 aggresome GO:0016604 nuclear body GO:0016605 PML body GO:0031514 motile cilium GO:0035770 ribonucleoprotein granule GO:0036126 sperm flagellum GO:0036464 cytoplasmic ribonucleoprotein granule GO:0044441 ciliary part GO:0044753 amphisome GO:0044754 autolysosome GO:0097223 sperm part GO:0097225 sperm midpiece

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04380 Osteoclast differentiation
Reactome	R-HSA-204998: Cell death signalling via NRAGE, NRIF and NADE R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-168256: Immune System R-HSA-446652: Interleukin-1 signaling R-HSA-5205647: Mitophagy R-HSA-209560: NF-kB is activated and signals survival R-HSA-205043: NRIF signals cell death from the nucleus R-HSA-5205685: Pink/Parkin Mediated Mitophagy R-HSA-162582: Signal Transduction R-HSA-449147: Signaling by Interleukins R-HSA-166520: Signalling by NGF R-HSA-193704: p75 NTR receptor-mediated signalling R-HSA-209543: p75NTR recruits signalling complexes R-HSA-193639: p75NTR signals via NF-kB

> KEGG and Reactome Pathway

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KEGG

hsa04380 Osteoclast differentiation

Reactome

R-HSA-204998: Cell death signalling via NRAGE, NRIF and NADE
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-168256: Immune System
R-HSA-446652: Interleukin-1 signaling
R-HSA-5205647: Mitophagy
R-HSA-209560: NF-kB is activated and signals survival
R-HSA-205043: NRIF signals cell death from the nucleus
R-HSA-5205685: Pink/Parkin Mediated Mitophagy
R-HSA-162582: Signal Transduction
R-HSA-449147: Signaling by Interleukins
R-HSA-166520: Signalling by NGF
R-HSA-193704: p75 NTR receptor-mediated signalling
R-HSA-209543: p75NTR recruits signalling complexes
R-HSA-193639: p75NTR signals via NF-kB

Summary
Symbol	SQSTM1
Name	sequestosome 1
Aliases	p62B; A170; PDB3; OSIL; Paget disease of bone 3; oxidative stress induced like; FTDALS3; EBI3-associated pro ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SQSTM1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between SQSTM1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27458013	Hepatocellular Carcinoma	Inhibit immunity	Innate immune responses are important for pathogen elimination and adaptive immune response activation. However, excess inflammation may contribute to immunopathology and disease progression (e.g. inflammation-associated hepatocellular carcinoma). Blockade of autophagy restored the immunosuppressive activity of patulin, and pharmacological activation of p62-dependent mitophagy directly reduced RIG-I-like receptor-dependent inflammatory cytokine production. These results demonstrated that p62-dependent mitophagy has an immunosuppressive role to innate immune response and might serve as a potential immunomodulatory target for inflammation-associated diseases.

Summary
Symbol	SQSTM1
Name	sequestosome 1
Aliases	p62B; A170; PDB3; OSIL; Paget disease of bone 3; oxidative stress induced like; FTDALS3; EBI3-associated pro ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of SQSTM1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	Second most enriched score: 0.54	Sensitive to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	SQSTM1
Name	sequestosome 1
Aliases	p62B; A170; PDB3; OSIL; Paget disease of bone 3; oxidative stress induced like; FTDALS3; EBI3-associated pro ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of SQSTM1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.204	0.595
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.7	0.847
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.152	0.953
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.024	0.945
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.106	0.971
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.19	0.96
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.221	0.651
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.015	0.994
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.42	0.863
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.082	0.975
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	-0.018	0.996
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.128	0.139

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of SQSTM1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	7.1	-7.1	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	2.7	1	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	3.4	0.3	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	0	11.1	0.36
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	0	25	0.364
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	SQSTM1
Name	sequestosome 1
Aliases	p62B; A170; PDB3; OSIL; Paget disease of bone 3; oxidative stress induced like; FTDALS3; EBI3-associated pro ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SQSTM1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	SQSTM1
Name	sequestosome 1
Aliases	p62B; A170; PDB3; OSIL; Paget disease of bone 3; oxidative stress induced like; FTDALS3; EBI3-associated pro ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SQSTM1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SQSTM1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SQSTM1
Name	sequestosome 1
Aliases	p62B; A170; PDB3; OSIL; Paget disease of bone 3; oxidative stress induced like; FTDALS3; EBI3-associated pro ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SQSTM1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	SQSTM1
Name	sequestosome 1
Aliases	p62B; A170; PDB3; OSIL; Paget disease of bone 3; oxidative stress induced like; FTDALS3; EBI3-associated pro ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SQSTM1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SQSTM1
Name	sequestosome 1
Aliases	p62B; A170; PDB3; OSIL; Paget disease of bone 3; oxidative stress induced like; FTDALS3; EBI3-associated pro ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SQSTM1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SQSTM1
Name	sequestosome 1
Aliases	p62B; A170; PDB3; OSIL; Paget disease of bone 3; oxidative stress induced like; FTDALS3; EBI3-associated pro ......
Chromosomal Location	5q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SQSTM1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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