LMPD Database

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LMP012442

UniProt Annotations

Entry Information
Gene Nameclusterin
Protein EntryCLUS_RAT
UniProt IDP05371
SpeciesRat
Comments
Comment typeDescription
Developmental StageExpressed by cells undergoing programmed death as a result of the hormonal stimuli or a traumatic insult.
FunctionFunctions 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)
PtmExtensively glycosylated with sulfated N-linked carbohydrates
PtmPolyubiquitinated, leading to proteasomal degradation
PtmProteolytically cleaved on its way through the secretory system, probably within the Golgi lumen
SimilarityBelongs to the clusterin family
Subcellular LocationSecreted {ECO:0000269|PubMed:3415696, ECO:0000269|PubMed:3651384}. Nucleus . Cytoplasm {ECO:0000250}. Mitochondrion membrane ; Peripheral membrane protein {ECO:0000250}; Cytoplasmic side . Cytoplasm, cytosol {ECO:0000250}. Microsome . Endoplasmic reticulum . Cytoplasmic vesicle, secretory vesicle, chromaffin granule . Note=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)
SubunitAntiparallel disulfide-linked heterodimer of an alpha chain and a beta chain. Self-associates and forms higher oligomers. Interacts with a broad range of misfolded proteins, including APP, APOC2 and LYZ. Slightly acidic pH promotes interaction with misfolded proteins. Forms high-molecular weight oligomers upon interaction with misfolded proteins. Interacts with APOA1, LRP2, CLUAP1 AND PON1. Interacts with the complement complex. Interacts with SYVN1, COMMD1, BTRC, CUL1 and with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes. Interacts (via alpha chain) with BAX in stressed cells, where BAX undergoes a conformation change leading to association with the mitochondrial membrane. Does not interact with BAX in unstressed cells. Interacts (via alpha chain) with XRCC6 (By similarity). Found in a complex with LTF, CLU, EPPIN and SEMG1 (By similarity)
Tissue SpecificityDetected in Sertoli cells (at protein level). Detected in cultured Sertoli cells, testis, epididymis, liver and brain