CLU
GeneName
CLU
Summary
CLU, also known as DAG, TRPM2, or gp80, is a 52 kDa glycoprotein that is widely expressed in various tissues, including the brain and immune cells. It is primarily localised to the extracellular region and is involved in several key biological processes such as amyloid-beta clearance, protein folding, and immune response regulation. CLU functions as a chaperone, binding to misfolded proteins and facilitating their clearance, while also playing a role in lipid metabolism and neuronal survival. Its interaction with amyloid-beta and tau proteins suggests a significant role in neurodegenerative diseases, particularly Alzheimer’s disease, where it may influence amyloid plaque formation and neurofibrillary tangle assembly.
Importance
CLU is relevant to: - Alzheimer’s disease research due to its involvement in amyloid-beta metabolism and clearance, potentially influencing disease progression. - Neuroinflammation and microglial activation, as it modulates immune responses in the central nervous system. - Protein misfolding disorders, given its role in chaperone-mediated protein folding and clearance of misfolded proteins. - Lipid metabolism and cardiovascular health, through its function in reverse cholesterol transport and low-density lipoprotein particle binding.
Top Products
For researchers investigating CLU, we recommend two excellent primary antibodies. The first is the well-cited polyclonal antibody, Anti-Clusterin antibody (ab69644), which has garnered 20 citations and is highly effective for Western blotting (WB), immunohistochemistry (IHC), and immunocytochemistry (ICC). This antibody is a trusted choice in the field. Additionally, we offer the recombinant antibody, Anti-Clusterin antibody [EPR2911] (ab92548), which has been validated in knockout models and is suitable for WB and IHC. With 12 citations, this monoclonal antibody provides the batch-to-batch consistency that researchers often seek. Together, these antibodies provide robust options for studying CLU in various applications. The Anti-Clusterin antibody [EPR2911] - Low endotoxin, Azide free (ab229445) is an excellent option for researchers looking to study CLU with high specificity and minimal interference.
Abcam Product Citation Summary
The data indicates that CLU is being studied in the context of HCV infection in human cells, highlighting its potential role in viral pathogenesis or cellular response to infection.
Abcam Product Citation Table
Function
Isoform 1
Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922, PubMed:12176985, PubMed:17260971, PubMed:19996109). Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro) (PubMed:12047389, PubMed:17407782, PubMed:17412999). Does not require ATP (PubMed:11123922). Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70 (PubMed:11123922). Does not refold proteins by itself (PubMed:11123922). Binding to cell surface receptors triggers internalization of the chaperone-client complex and subsequent lysosomal or proteasomal degradation (PubMed:21505792). Protects cells against apoptosis and against cytolysis by complement: inhibits assembly of the complement membrane attack complex (MAC) by preventing polymerization of C9 pore component of the MAC complex (PubMed:2780565, PubMed:1903064, PubMed:2601725, PubMed:2721499, PubMed:1551440, PubMed:9200695, PubMed:34667172). 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 (PubMed:20068069). Promotes proteasomal degradation of COMMD1 and IKBKB (PubMed:20068069). Modulates NF-kappa-B transcriptional activity (PubMed:12882985). A mitochondrial form suppresses BAX-dependent release of cytochrome c into the cytoplasm and inhibit apoptosis (PubMed:16113678, PubMed:17689225). Plays a role in the regulation of cell proliferation (PubMed:19137541). An intracellular form suppresses stress-induced apoptosis by stabilizing mitochondrial membrane integrity through interaction with HSPA5 (PubMed:22689054). Secreted form does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (PubMed:24073260). Secreted form act as an important modulator during neuronal differentiation through interaction with STMN3 (By similarity). Plays a role in the clearance of immune complexes that arise during cell injury (By similarity).
Isoform 6
Does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity.
Isoform 4
Does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (PubMed:24073260). Promotes cell death through interaction with BCL2L1 that releases and activates BAX (PubMed:21567405).
Post-translational modifications
Proteolytically cleaved on its way through the secretory system, probably within the Golgi lumen (PubMed:2387851). Proteolytic cleavage is not necessary for its chaperone activity (PubMed:25402950). All non-secreted forms are not proteolytically cleaved (PubMed:24073260). Chaperone activity of uncleaved forms is dependent on a non-reducing environment (PubMed:25402950).
Polyubiquitinated, leading to proteasomal degradation (PubMed:17451556, PubMed:19137541). Under cellular stress, the intracellular level of cleaved form is reduced due to proteasomal degradation (PubMed:17451556).
Extensively glycosylated with sulfated N-linked carbohydrates (PubMed:17260971, PubMed:2387851). About 30% of the protein mass is comprised of complex N-linked carbohydrate (PubMed:2387851). Endoplasmic reticulum (ER) stress induces changes in glycosylation status and increases level of hypoglycosylated forms (PubMed:22689054). Core carbohydrates are essential for chaperone activity (PubMed:25402950). Non-secreted forms are hypoglycosylated or unglycosylated (PubMed:24073260).
Sequence Similarities
Belongs to the clusterin family.
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.
Cellular localization
- Isoform 1
- Secreted
- Can retrotranslocate from the secretory compartments to the cytosol upon cellular stress.
- Isoform 4
- Cytoplasm
- Keeps cytoplasmic localization in stressed and unstressed cell.
- Isoform 6
- Cytoplasm
- Keeps cytoplasmic localization in stressed and unstressed cell.
- Nucleus
- Cytoplasm
- Mitochondrion membrane
- Peripheral membrane protein
- Cytoplasmic side
- Cytoplasm
- Cytosol
- Microsome
- Endoplasmic reticulum
- Mitochondrion
- Mitochondrion membrane
- Cytoplasm
- Perinuclear region
- Cytoplasmic vesicle
- Secretory vesicle
- Chromaffin granule
- Secreted isoforms can retrotranslocate from the secretory compartments to the cytosol upon cellular stress (PubMed:17451556). Detected in perinuclear foci that may be aggresomes containing misfolded, ubiquitinated proteins (PubMed:20068069). Detected at the mitochondrion membrane upon induction of apoptosis (PubMed:17689225). Under ER stress, a immaturely glycosylated pre-secreted form retrotranslocates from the endoplasmic reticulum (ER)-Golgi network to the cytoplasm to localize in the mitochondria through HSPA5 interaction (PubMed:22689054). ER stress reduces secretion (PubMed:22689054). Under the stress, minor amounts of non-secreted forms accumulate in cytoplasm (PubMed:17451556, PubMed:22689054, PubMed:24073260). Non-secreted forms emerge mainly from failed translocation, alternative splicing or non-canonical initiation start codon (PubMed:12551933, PubMed:24073260).
Alternative names
APOJ, CLI, KUB1, AAG4, CLU, Clusterin, Aging-associated gene 4 protein, Apolipoprotein J, Complement cytolysis inhibitor, Ku70-binding protein 1, NA1/NA2, Sulfated glycoprotein 2, Testosterone-repressed prostate message 2, Apo-J, SGP-2, TRPM-2