Summary of CLU
CLU encodes a protein that is a secreted chaperone that is involved in several events such as cell death, tumor progression, and neurodegenerative disorders (R).
The Function of CLU
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.
Protein names
Recommended name:
ClusterinShort name:
CLIAlternative name(s):
Aging-associated gene 4 proteinApolipoprotein J
Apo-J
Complement cytolysis inhibitor
Complement-associated protein SP-40,40
Ku70-binding protein 1
NA1/NA2
Testosterone-repressed prostate message 2
TRPM-2
ApoJalpha
Complement cytolysis inhibitor a chain
ApoJbeta
Complement cytolysis inhibitor b chain
- RS11136000 (CLU) ??
- RS1532278 (CLU) ??
- RS17466684 (CLU) ??
- RS2279590 (CLU) ??
- RS569214 (CLU) ??
- RS9331888 (CLU) ??
- RS9331896 (CLU) ??
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Top Gene-Substance Interactions
CLU Interacts with These Diseases
| Disease | Score |
Substances That Increase CLU
| Substances | Interaction | Organism | Category |
Substances That Decrease CLU
| Substances | Interaction | Organism | Category |
Conditions with Increased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
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.
Gene Pathways:
Induction:
Up-regulated in response to enterovirus 71 (EV71) infection (at protein level). Up-regulated by agents that induce apoptosis, both at mRNA and protein level. Isoform 1 is up-regulated by androgen. Isoform 2 is down-regulated by androgen.
Molecular Function:
Biological Processes:
- Cell Morphogenesis
- Microglial Cell Activation
- Release Of Cytochrome C From Mitochondria
- Platelet Degranulation
- Lipid Metabolic Process
- Complement Activation
- Complement Activation, Classical Pathway
- Aging
- Positive Regulation Of Cell Proliferation
- Response To Light Stimulus
- Response To Wounding
- Response To Virus
- Protein Import
- Endocrine Pancreas Development
- Central Nervous System Myelin Maintenance
- Positive Regulation Of Proteasomal Ubiquitin-Dependent Protein Catabolic Process
- Negative Regulation Of Protein Homooligomerization
- Positive Regulation Of Tumor Necrosis Factor Production
- Response To Potassium Ion
- Positive Regulation Of Apoptotic Process
- Reverse Cholesterol Transport
- Estrous Cycle
- Innate Immune Response
- Positive Regulation Of Nitric Oxide Biosynthetic Process
- Positive Regulation Of Cell Differentiation
- Neuron Projection Morphogenesis
- Protein Stabilization
- Positive Regulation Of Nf-Kappab Transcription Factor Activity
- Chaperone-Mediated Protein Complex Assembly
- Response To Misfolded Protein
- Chaperone-Mediated Protein Folding
- Microglial Cell Proliferation
- Cellular Response To Growth Factor Stimulus
- Intrinsic Apoptotic Signaling Pathway
- Regulation Of Beta-Amyloid Clearance
- Regulation Of Neuron Death
- Positive Regulation Of Neuron Death
- Positive Regulation Of Beta-Amyloid Formation
- Negative Regulation Of Intrinsic Apoptotic Signaling Pathway In Response To Dna Damage
- Negative Regulation Of Beta-Amyloid Formation
- Regulation Of Neuronal Signal Transduction
- Positive Regulation Of Tau-Protein Kinase Activity
- Positive Regulation Of Neurofibrillary Tangle Assembly
- Positive Regulation Of Protein Ubiquitination Involved In Ubiquitin-Dependent Protein Catabolic Process
- Positive Regulation Of Intrinsic Apoptotic Signaling Pathway