Clu
entrez
24854
canonical
uniprot
P05371
canonical
ensembl
ENSRNOG00000016460
resolver
ensp
ENSRNOP00000072116
resolver
enst
ENSRNOT00000078861
resolver
genesymbol
Clu
resolver
uniprot
A0A0G2K259
resolver
uniprot_entry
A0A0G2K259_RAT
resolver
uniprot_entry
CLUS_RAT
resolver
amino_acid_sequence
MKILLLCVALLLTWDNGMVLGEQEFSDNELQELSTQGSRYVNKEIQNAVQGVKHIKTLIEKTNAERKSLLNSLEEAKKKKEGALDDTRDSEMKLKAFPEVCNETMMALWEECKPCLKHTCMKFYARVCRSGSGLVGRQLEEFLNQSSPFYFWMNGDRIDSLLESDRQQSQVLDAMQDSFTRASGIIDTLFQDRFFTHEPQDIHHFSPMGFPHKRPHFLYPKSRLVRSLMPLSHYGPLSFHNMFQPFFDMIHQAQQAMDVQLHSPALQFPDVDFLKEGEDDPTVCKEIRHNSTGCLKMKGQCEKCQEILSVDCSTNNPAQANLRQELNDSLQVAERLTQQYNELLHSLQSKMLNTSSLLEQLNDQFTWVSQLANLTQGDDQYLRVSTVTTHSSDSEVPSRVTEVVVKLFDSDPITVVLPEEVSKDNPKFMDTVAEKALQEYRRKSRME
uniprot
proteins
function
FUNCTION: Functions as extracellular chaperone that prevents aggregation of non native 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: inhibits assembly of the complement membrane attack complex (MAC) by preventing polymerization of C9 pore component of the MAC complex. 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 (By similarity). Following stress, promotes apoptosis (By similarity). 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. An intracellular form suppresses stress-induced apoptosis by stabilizing mitochondrial membrane integrity through interaction with HSPA5. Secreted form does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (By similarity). Secreted form act as an important modulator during neuronal differentiation through interaction with STMN3 (PubMed:16038898). Plays a role in the clearance of immune complexes that arise during cell injury (By similarity). {ECO:0000250|UniProtKB:P10909, ECO:0000250|UniProtKB:Q06890, ECO:0000269|PubMed:16038898}.
uniprot
proteins
mass_dalton
51375
uniprot
proteins
post_translational_modification
PTM: Proteolytically cleaved on its way through the secretory system, probably within the Golgi lumen (PubMed:3415696, PubMed:3651384). Proteolytic cleavage is not necessary for its chaperone activity. All non-secreted forms are not proteolytically cleaved. Chaperone activity of uncleaved forms is dependent on a non-reducing environment (By similarity). {ECO:0000250|UniProtKB:P10909, ECO:0000269|PubMed:3415696, ECO:0000269|PubMed:3651384}.; PTM: Polyubiquitinated, leading to proteasomal degradation. Under cellular stress, the intracellular level of cleaved form is reduced due to proteasomal degradation. {ECO:0000250|UniProtKB:P10909}.; PTM: Extensively glycosylated with sulfated N-linked carbohydrates (PubMed:3651384). About 30% of the protein mass is comprised of complex N-linked carbohydrate. Endoplasmic reticulum (ER) stress induces changes in glycosylation status and increases level of hypoglycosylated forms. Core carbohydrates are essential for chaperone activity. Non-secreted forms are hypoglycosylated or unglycosylated (By similarity). {ECO:0000250|UniProtKB:P10909, ECO:0000269|PubMed:3651384}.
uniprot
proteins
protein_family
Clusterin family
uniprot
proteins
pubmed
16038898
uniprot
proteins
pubmed
22673903
uniprot
proteins
pubmed
2299741
uniprot
proteins
pubmed
2920020
uniprot
proteins
pubmed
3415696
uniprot
proteins
pubmed
3651384
uniprot
proteins
pubmed
7680346
uniprot
proteins
sequence_length
447
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:3415696, ECO:0000269|PubMed:3651384}. Nucleus {ECO:0000250|UniProtKB:P10909}. Cytoplasm {ECO:0000250|UniProtKB:P10909}. Mitochondrion membrane {ECO:0000250|UniProtKB:P10909}; Peripheral membrane protein {ECO:0000250|UniProtKB:P10909}; Cytoplasmic side {ECO:0000250|UniProtKB:P10909}. Cytoplasm, cytosol {ECO:0000269|PubMed:16038898}. Microsome {ECO:0000250|UniProtKB:P10909}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P10909}. Mitochondrion {ECO:0000250|UniProtKB:P10909}. Mitochondrion membrane {ECO:0000250|UniProtKB:P10909}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:16038898}. 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. 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. ER stress reduces secretion. Under the stress, minor amounts of non-secreted forms accumulate in cytoplasm. {ECO:0000250|UniProtKB:P10909}.
uniprot
proteins