InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SQSTM1

Summary

InnateDB Protein

IDBP-61895.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SQSTM1

Protein Name

sequestosome 1

Synonyms

A170; OSIL; p60; p62; p62B; PDB3; ZIP3;

Species

Homo sapiens

Ensembl Protein

ENSP00000353944

InnateDB Gene

IDBG-61811 (SQSTM1)

Protein Structure

UniProt Annotation

Function

Autophagy receptor that interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family. Required both for the formation and autophagic degradation of polyubiquitin-containing bodies, called ALIS (aggresome-like induced structures) and links ALIS to the autophagic machinery. Involved in midbody ring degradation. 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. {ECO:0000250, ECO:0000269PubMed:10356400, ECO:0000269PubMed:10747026, ECO:0000269PubMed:11244088, ECO:0000269PubMed:12471037, ECO:0000269PubMed:15340068, ECO:0000269PubMed:15802564, ECO:0000269PubMed:15911346, ECO:0000269PubMed:15953362, ECO:0000269PubMed:16079148, ECO:0000269PubMed:16286508, ECO:0000269PubMed:19931284, ECO:0000269PubMed:20168092, ECO:0000269PubMed:24128730}.

Subcellular Localization

Cytoplasm. Late endosome. Lysosome. Cytoplasmic vesicle, autophagosome. Nucleus. Endoplasmic reticulum. Cytoplasm, P-body. Note=Sarcomere (By similarity). In cardiac muscles 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 the cytoplasmic bodies. {ECO:0000250}.

Disease Associations

Paget disease of bone (PDB) [MIM:602080]: Metabolic bone disease affecting the axial skeleton and characterized by focal areas of increased and disorganized bone turn-over due to activated osteoclasts. Manifestations of the disease include bone pain, deformity, pathological fractures, deafness, neurological complications and increased risk of osteosarcoma. PDB is a chronic disease affecting 2 to 3% of the population above the age of 40 years. {ECO:0000269PubMed:11992264, ECO:0000269PubMed:12374763, ECO:0000269PubMed:14584883, ECO:0000269PubMed:15125799, ECO:0000269PubMed:15146436, ECO:0000269PubMed:15176995, ECO:0000269PubMed:15207768}. Note=The disease is caused by mutations affecting the gene represented in this entry.Note=In a cell model for Huntington disease (HD), appears to form a shell surrounding aggregates of mutant HTT that may protect cells from apoptosis, possibly by recruiting autophagosomal components to the polyubiquitinated protein aggregates.

Tissue Specificity

Ubiquitously expressed. {ECO:0000269PubMed:8650207}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 502 experimentally validated interaction(s) in this database.
They are also associated with 31 interaction(s) predicted by orthology.

Experimentally validated
Total	502 [view]
Protein-Protein	498 [view]
Protein-DNA	4 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	31 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004674	protein serine/threonine kinase activity
GO:0005080	protein kinase C binding
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0019901	protein kinase binding
GO:0030971	receptor tyrosine kinase binding
GO:0042169	SH2 domain binding
GO:0042802	identical protein binding
GO:0043130	ubiquitin binding

Biological Process

GO:0002376	immune system process
GO:0006468	protein phosphorylation
GO:0006511	ubiquitin-dependent protein catabolic process
GO:0006914	autophagy
GO:0006950	response to stress
GO:0008104	protein localization
GO:0016197	endosomal transport
GO:0016236	macroautophagy
GO:0016239	positive regulation of macroautophagy
GO:0030154	cell differentiation
GO:0035556	intracellular signal transduction
GO:0043065	positive regulation of apoptotic process
GO:0043066	negative regulation of apoptotic process
GO:0043122	regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045087	innate immune response (InnateDB)
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046578	regulation of Ras protein signal transduction
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0097190	apoptotic signaling pathway

Cellular Component

GO:0000932	cytoplasmic mRNA processing body
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005764	lysosome
GO:0005770	late endosome
GO:0005776	autophagic vacuole
GO:0005783	endoplasmic reticulum
GO:0005829	cytosol
GO:0016234	inclusion body
GO:0016605	PML body
GO:0031410	cytoplasmic vesicle
GO:0070062	extracellular vesicular exosome