InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CLU

Summary

InnateDB Protein

IDBP-484941.4

Last Modified

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

Gene Symbol

CLU

Protein Name

clusterin

Synonyms

APO-J; APOJ; CLI; CLU1; CLU2; KUB1; NA1/NA2; SGP-2; SGP2; SP-40; TRPM-2; TRPM2;

Species

Homo sapiens

Ensembl Protein

ENSP00000429620

InnateDB Gene

IDBG-14287 (CLU)

Protein Structure

UniProt Annotation

Function

Isoform 1 functions as extracellular chaperone that prevents aggregation of nonnative proteins. Prevents stress- induced aggregation of blood plasma proteins. Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro). Does not require ATP. Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70. Does not refold proteins by itself. Binding to cell surface receptors triggers internalization of the chaperone-client complex and subsequent lysosomal or proteasomal degradation. Secreted isoform 1 protects cells against apoptosis and against cytolysis by complement. Intracellular isoforms interact with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes and promote the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes proteasomal degradation of COMMD1 and IKBKB. Modulates NF-kappa-B transcriptional activity. Nuclear isoforms promote apoptosis. Mitochondrial isoforms suppress BAX-dependent release of cytochrome c into the cytoplasm and inhibit apoptosis. Plays a role in the regulation of cell proliferation. {ECO:0000269PubMed:11123922, ECO:0000269PubMed:12047389, ECO:0000269PubMed:12176985, ECO:0000269PubMed:12551933, ECO:0000269PubMed:12882985, ECO:0000269PubMed:16113678, ECO:0000269PubMed:17260971, ECO:0000269PubMed:17407782, ECO:0000269PubMed:17412999, ECO:0000269PubMed:17689225, ECO:0000269PubMed:19137541, ECO:0000269PubMed:19535339, ECO:0000269PubMed:19996109, ECO:0000269PubMed:20068069, ECO:0000269PubMed:21505792}.

Subcellular Localization

Isoform 1: Secreted. Note=Can retrotranslocate from the secretory compartments to the cytosol upon cellular stress.Nucleus. Cytoplasm. Mitochondrion membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm, cytosol. Microsome. Endoplasmic reticulum. Cytoplasmic vesicle, secretory vesicle, chromaffin granule {ECO:0000250}. Note=Isoforms lacking the N-terminal signal sequence have been shown to be cytoplasmic and/or nuclear. Secreted isoforms can retrotranslocate from the secretory compartments to the cytosol upon cellular stress. Detected in perinuclear foci that may be aggresomes containing misfolded, ubiquitinated proteins. Detected at the mitochondrion membrane upon induction of apoptosis.

Disease Associations

Tissue Specificity

Detected in blood plasma, cerebrospinal fluid, milk, seminal plasma and colon mucosa. Detected in the germinal center of colon lymphoid nodules and in colon parasympathetic ganglia of the Auerbach plexus (at protein level). Ubiquitous. Detected in brain, testis, ovary, liver and pancreas, and at lower levels in kidney, heart, spleen and lung. {ECO:0000269PubMed:11123922, ECO:0000269PubMed:17260971, ECO:0000269PubMed:17322305, ECO:0000269PubMed:17412999, ECO:0000269PubMed:1974459, ECO:0000269PubMed:2387851, ECO:0000269PubMed:2780565, ECO:0000269PubMed:3154963, ECO:0000269PubMed:8181474, ECO:0000269PubMed:8292612, ECO:0000269PubMed:8328966}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 96 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	96 [view]
Protein-Protein	92 [view]
Protein-DNA	4 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0031625	ubiquitin protein ligase binding
GO:0051787	misfolded protein binding

Biological Process

GO:0000902	cell morphogenesis
GO:0001774	microglial cell activation
GO:0001836	release of cytochrome c from mitochondria
GO:0002576	platelet degranulation
GO:0006629	lipid metabolic process
GO:0006956	complement activation
GO:0006958	complement activation, classical pathway
GO:0007596	blood coagulation
GO:0008219	cell death
GO:0009615	response to virus
GO:0017038	protein import
GO:0030168	platelet activation
GO:0032286	central nervous system myelin maintenance
GO:0032436	positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032463	negative regulation of protein homooligomerization
GO:0032760	positive regulation of tumor necrosis factor production
GO:0043065	positive regulation of apoptotic process
GO:0043691	reverse cholesterol transport
GO:0045087	innate immune response
GO:0045429	positive regulation of nitric oxide biosynthetic process
GO:0050821	protein stabilization
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0051131	chaperone-mediated protein complex assembly
GO:0051788	response to misfolded protein
GO:0061077	chaperone-mediated protein folding
GO:0061518	microglial cell proliferation
GO:0097193	intrinsic apoptotic signaling pathway
GO:1900221	regulation of beta-amyloid clearance
GO:1901214	regulation of neuron death
GO:1901216	positive regulation of neuron death
GO:1902004	positive regulation of beta-amyloid formation
GO:1902230	negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage
GO:1902430	negative regulation of beta-amyloid formation
GO:1902847	regulation of neuronal signal transduction
GO:1902949	positive regulation of tau-protein kinase activity
GO:1902998	positive regulation of neurofibrillary tangle assembly
GO:2000060	positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:2001244	positive regulation of intrinsic apoptotic signaling pathway

Cellular Component

GO:0005576	extracellular region
GO:0005615	extracellular space
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005783	endoplasmic reticulum
GO:0005829	cytosol
GO:0031012	extracellular matrix
GO:0031093	platelet alpha granule lumen
GO:0031966	mitochondrial membrane
GO:0034366	spherical high-density lipoprotein particle
GO:0042583	chromaffin granule
GO:0048471	perinuclear region of cytoplasm
GO:0070062	extracellular vesicular exosome
GO:0072562	blood microparticle
GO:0097418	neurofibrillary tangle
GO:0097440	apical dendrite