CLU Antibody – Mouse Monoclonal

The protein encoded by this gene is a secreted chaperone that can under some stress conditions also be found in the cell cytosol. It has been suggested to be involved in several basic biological events such as cell death, tumor progression, and neurodegenerative disorders. Alternate splicing results in both coding and non-coding variants.[provided by RefSeq, May 2011]

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. Belongs to the clusterin family. 5 isoforms of the human protein are produced by alternative splicing.

Protein type: Apoptosis; Secreted, signal peptide; Mitochondrial; Secreted

Chromosomal Location of Human Ortholog: 8p21-p12

Cellular Component: extracellular matrix; Golgi apparatus; extracellular space; mitochondrion; endoplasmic reticulum; perinuclear region of cytoplasm; cytoplasm; mitochondrial membrane; extracellular region; cytosol; nucleus

Molecular Function: protein binding; chaperone binding; ubiquitin protein ligase binding; ATPase activity; misfolded protein binding

Biological Process: platelet activation; response to misfolded protein; release of cytochrome c from mitochondria; positive regulation of nitric oxide biosynthetic process; protein stabilization; positive regulation of apoptosis; response to virus; cell morphogenesis; microglial cell activation; positive regulation of tumor necrosis factor production; activation of NF-kappaB transcription factor; complement activation; negative regulation of protein homooligomerization; platelet degranulation; reverse cholesterol transport; myelin maintenance in the central nervous system; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; protein import; innate immune response; lipid metabolic process; blood coagulation; chaperone-mediated protein complex assembly; complement activation, classical pathway