Human Clusterin, CLU ELI

[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: 17412999, PubMed: 17407782).

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 (PubMed: 2780565).

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).