InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Gene: SQSTM1

Summary

InnateDB Gene

IDBG-61811.6

Last Modified

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

Gene Symbol

SQSTM1

Gene Name

sequestosome 1

Synonyms

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

Species

Homo sapiens

Ensembl Gene

ENSG00000161011

Encoded Proteins

IDBP-61819

sequestosome 1

IDBP-61895

sequestosome 1

IDBP-382603

sequestosome 1

IDBP-382609

sequestosome 1

IDBP-477305

sequestosome 1

IDBP-473760

sequestosome 1

IDBP-478633

sequestosome 1

IDBP-478384

sequestosome 1

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 19812211

SQSTM1 (p62) targets invading bacteria to the autophagy pathway and its expression is required for efficient autophagy of bacteria, as well as restriction of their intracellular replication.

PMID 19850933

SQSTM1 is a key intracellular target of innate defence regulator-1 (IDR-1), a synthetic peptide.

PMID 20206555

SQSTM1 has bactericidal properties where it brings cytosolic proteins to autolysosomes where they are processed from innocuous precursors into neo-antimicrobial peptides.

PMID 20837465

SQSTM1 and HDAC6 are important determinants of aggregated localization of MyD88 and MyD88 activation initiates a polyubiquitinated protein accumulating pathway that modulates MyD88-dependent signal transduction.

PMID 21220332

SQSTM1 is required for TLR4-mediated autophagy. TLR4-driven induction of SQSTM1 plays an essential role in the formation and the autophagy degradation of aggresome-like induced structures, which might be critical for regulating host defence.

PMID 22901810

SQSTM1 and CALCOCO2 are ubiquitin-autophagy receptors that are required for the recognition of extracelluar bacterial DNA by the TMEM173 (STING)-dependent cytosolic pathway, marking bacteria with ubiquitin, and delivery of bacilli to autophagosomes. (Demonstrated in mouse)

InnateDB Annotation from Orthologs

Summary

PMID 21220332

[Mus musculus] Sqstm1 is required for Tlr4-mediated autophagy. Tlr4-driven induction of Sqstm1 plays an essential role in the formation and the autophagy degradation of aggresome-like induced structures, which might be critical for regulating host defense.

PMID 22901810

[Mus musculus] Sqstm1 and Calcoco2 are ubiquitin-autophagy receptors that are required for the recognition of extracelluar bacterial DNA by the Tmem173 (STING)-dependent cytosolic pathway, marking bacteria with ubiquitin, and delivery of bacilli to autophagosomes.

PMID 24011591

[Mus musculus] Phosphorylation of Sqstm1 (p62) activates the Keap1-Nrf2 pathway during selective autophagy.

PMID 25609235

[Mus musculus] Sqstm1 captures Tnfaip3, an NFkB inhibitor, and sequesters it in the autophagosome. This allows macrophages to release chemokines that recruit neutrophils and boost antifungal immunity.

Entrez Gene

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]

Gene Information

Type

Protein coding

Genomic Location

Chromosome 5:179806398-179838078

Strand

Forward strand

Band

q35.3

Transcripts

ENST00000389805	ENSP00000374455
ENST00000360718	ENSP00000353944
ENST00000422245	ENSP00000394534
ENST00000453046	ENSP00000405061
ENST00000506042
ENST00000514093	ENSP00000427308
ENST00000506690
ENST00000512234
ENST00000481335
ENST00000464493
ENST00000508284	ENSP00000424195
ENST00000504627	ENSP00000425957
ENST00000510187	ENSP00000424477
ENST00000485412
ENST00000466342

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:0042803	protein homodimerization activity
GO:0043130	ubiquitin binding
GO:0070530	K63-linked polyubiquitin binding

Biological Process

GO:0001934	positive regulation of protein phosphorylation
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:0051291	protein heterooligomerization
GO:0097190	apoptotic signaling pathway

Cellular Component

GO:0000407	pre-autophagosomal structure
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:0016235	aggresome
GO:0016605	PML body
GO:0031410	cytoplasmic vesicle
GO:0070062	extracellular vesicular exosome