Version 5.4
Bos taurus Protein: CLU
Summary
InnateDB Protein IDBP-681173.2
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol CLU
Protein Name ClusterinClusterin beta chainClusterin alpha chain
Synonyms gpIII;
Species Bos taurus
Ensembl Protein ENSBTAP00000007324
InnateDB Gene IDBG-629759 (CLU)
Protein Structure
UniProt Annotation
Function 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. When secreted, protects cells against apoptosis and against cytolysis by complement. Intracellular forms 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. Promotes apoptosis when in the nucleus. Inhibits apoptosis when associated with the mitochondrial membrane by interference with BAX-dependent release of cytochrome c into the cytoplasm. Plays a role in the regulation of cell proliferation (By similarity). {ECO:0000250}.
Subcellular Localization Secreted {ECO:0000250}. Cytoplasmic vesicle, secretory vesicle, chromaffin granule. Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. Mitochondrion membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Cytoplasm, cytosol {ECO:0000250}. Microsome {ECO:0000250}. Endoplasmic reticulum {ECO:0000250}. Note=Present in chromaffin granules. 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 (By similarity). {ECO:0000250}.
Disease Associations
Tissue Specificity Expressed abundantly in liver, testis, and brain.
Comments
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 1 experimentally validated interaction(s) in this database.
They are also associated with 62 interaction(s) predicted by orthology.
Experimentally validated
Total 1 [view]
Protein-Protein 1 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 62 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0031625 ubiquitin protein ligase binding
GO:0051787 misfolded protein binding
Biological Process
GO:0008219 cell death
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032463 negative regulation of protein homooligomerization
GO:0043065 positive regulation of apoptotic process
GO:0050821 protein stabilization
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051788 response to misfolded protein
GO:0061077 chaperone-mediated protein folding
GO:0097193 intrinsic apoptotic signaling pathway
GO:1902230 negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage
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:0016020 membrane
GO:0031012 extracellular matrix
GO:0031410 cytoplasmic vesicle
GO:0031966 mitochondrial membrane
GO:0034366 spherical high-density lipoprotein particle
GO:0042583 chromaffin granule
GO:0043231 intracellular membrane-bounded organelle
GO:0048471 perinuclear region of cytoplasm
Protein Structure and Domains
PDB ID
InterPro IPR000753 Clusterin-like
IPR016014 Clusterin, N-terminal
IPR016015 Clusterin, C-terminal
IPR016016 Clusterin
PFAM PF01093
PRINTS
PIRSF PIRSF002368
SMART SM00030
SM00035
TIGRFAMs
Post-translational Modifications
Modification
Cross-References
SwissProt P17697
PhosphoSite PhosphoSite-
TrEMBL
UniProt Splice Variant
Entrez Gene 280750
UniGene Bt.95502
RefSeq NP_776327
HUGO
OMIM
CCDS
HPRD
IMGT
EMBL BC118223 BC149632 BT030502 J05391
GenPept AAA30554 AAI18224 AAI49633 ABQ12942

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

InnateDB is being developed jointly by the Brinkman Laboratory (Simon Fraser University, British Columbia, Canada), the Hancock Laboratory (University of British Columbia, Vancouver, British Columbia) and the Lynn EMBL Australia Group (South Australian Health & Medical Research Institute and Flinders University, Adelaide, Australia).

Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca