CLU
entrez
1191
canonical
uniprot
P10909
canonical
ensembl
ENSG00000120885
resolver
ensp
ENSP00000315130
resolver
genesymbol
CLU
resolver
genesymbol_syn
APOJ
resolver
genesymbol_syn
CLI
resolver
genesymbol_syn
KUB1
resolver
hgnc
HGNC:2095
resolver
uniprot
B2R9Q1
resolver
uniprot
B3KSE6
resolver
uniprot
P11380
resolver
uniprot
P11381
resolver
uniprot
Q2TU75
resolver
uniprot
Q5HYC1
resolver
uniprot
Q7Z5B9
resolver
uniprot_entry
CLUS_HUMAN
resolver
uniprot_sec
B2R9Q1
resolver
uniprot_sec
B3KSE6
resolver
uniprot_sec
P11380
resolver
uniprot_sec
P11381
resolver
uniprot_sec
Q2TU75
resolver
uniprot_sec
Q5HYC1
resolver
uniprot_sec
Q7Z5B9
resolver
amino_acid_sequence
MMKTLLLFVGLLLTWESGQVLGDQTVSDNELQEMSNQGSKYVNKEIQNAVNGVKQIKTLIEKTNEERKTLLSNLEEAKKKKEDALNETRESETKLKELPGVCNETMMALWEECKPCLKQTCMKFYARVCRSGSGLVGRQLEEFLNQSSPFYFWMNGDRIDSLLENDRQQTHMLDVMQDHFSRASSIIDELFQDRFFTREPQDTYHYLPFSLPHRRPHFFFPKSRIVRSLMPFSPYEPLNFHAMFQPFLEMIHEAQQAMDIHFHSPAFQHPPTEFIREGDDDRTVCREIRHNSTGCLRMKDQCDKCREILSVDCSTNNPSQAKLRRELDESLQVAERLTRKYNELLKSYQWKMLNTSSLLEQLNEQFNWVSRLANLTQGEDQYYLRVTTVASHTSDSDVPSGVTEVVVKLFDSDPITVTVPVEVSRKNPKFMETVAEKALQEYRKKHREE
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:P05371, ECO:0000250|UniProtKB:Q06890, ECO:0000269|PubMed:11123922, ECO:0000269|PubMed:12047389, ECO:0000269|PubMed:12176985, ECO:0000269|PubMed:12882985, ECO:0000269|PubMed:1551440, ECO:0000269|PubMed:16113678, ECO:0000269|PubMed:17260971, ECO:0000269|PubMed:17407782, ECO:0000269|PubMed:17412999, ECO:0000269|PubMed:17689225, ECO:0000269|PubMed:1903064, ECO:0000269|PubMed:19137541, ECO:0000269|PubMed:19535339, ECO:0000269|PubMed:19996109, ECO:0000269|PubMed:20068069, ECO:0000269|PubMed:21505792, ECO:0000269|PubMed:22689054, ECO:0000269|PubMed:24073260, ECO:0000269|PubMed:2601725, ECO:0000269|PubMed:2721499, ECO:0000269|PubMed:2780565, ECO:0000269|PubMed:34667172, ECO:0000269|PubMed:9200695}.; FUNCTION: [Isoform 6]: Does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity. {ECO:0000269|PubMed:24073260}.; FUNCTION: [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). {ECO:0000269|PubMed:21567405, ECO:0000269|PubMed:24073260}.
uniprot
proteins
mass_dalton
52495
uniprot
proteins
mutagenesis
MUTAGEN 86; /note="N->Q: Decreases molecular mass of beta chain; when associated with Q-103 and Q-145."; /evidence="ECO:0000269|PubMed:22689054"; MUTAGEN 103; /note="N->Q: Decreases molecular mass of beta chain; when associated with Q-86 and Q-145."; /evidence="ECO:0000269|PubMed:22689054"; MUTAGEN 145; /note="N->Q: Decreases molecular mass of beta chain; when associated with Q-86 and Q-103."; /evidence="ECO:0000269|PubMed:22689054"; MUTAGEN 226; /note="V->T: Does not affect proteolytic cleavage."; /evidence="ECO:0000269|PubMed:25402950"; MUTAGEN 227; /note="R->Q: Affects proteolytic cleavage."; /evidence="ECO:0000269|PubMed:25402950"; MUTAGEN 291; /note="N->Q: Decreases molecular mass of alpha chain; when associated with Q-354 and Q-374. Decreases secretion; when associated with Q-354 and Q-374."; /evidence="ECO:0000269|PubMed:22689054"; MUTAGEN 354; /note="N->Q: Decreases molecular mass of alpha chain; when associated with Q-291 and Q-374. Decreases secretion; when associated with Q-291 and Q-374."; /evidence="ECO:0000269|PubMed:22689054"; MUTAGEN 374; /note="N->Q: Decreases molecular mass of alpha chain; when associated with Q-291 and Q-354. Decreases secretion; when associated with Q-291 and Q-354."; /evidence="ECO:0000269|PubMed:22689054
uniprot
proteins
post_translational_modification
PTM: 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). {ECO:0000269|PubMed:2387851, ECO:0000269|PubMed:24073260, ECO:0000269|PubMed:25402950}.; PTM: 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). {ECO:0000269|PubMed:17451556, ECO:0000269|PubMed:19137541}.; PTM: 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). {ECO:0000269|PubMed:17260971, ECO:0000269|PubMed:22689054, ECO:0000269|PubMed:2387851, ECO:0000269|PubMed:24073260, ECO:0000269|PubMed:25402950}.
uniprot
proteins
protein_family
Clusterin family
uniprot
proteins
pubmed
11123922
uniprot
proteins
pubmed
12047389
uniprot
proteins
pubmed
12176985
uniprot
proteins
pubmed
12551933
uniprot
proteins
pubmed
12754519
uniprot
proteins
pubmed
12882985
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14760718
uniprot
proteins
pubmed
1491011
uniprot
proteins
pubmed
15480429
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
1551440
uniprot
proteins
pubmed
16113678
uniprot
proteins
pubmed
16263699
uniprot
proteins
pubmed
16335952
uniprot
proteins
pubmed
16421571
uniprot
proteins
pubmed
16548883
uniprot
proteins
pubmed
16740002
uniprot
proteins
pubmed
17148459
uniprot
proteins
pubmed
17260971
uniprot
proteins
pubmed
17322305
uniprot
proteins
pubmed
17407782
uniprot
proteins
pubmed
17412999
uniprot
proteins
pubmed
1742316
uniprot
proteins
pubmed
17451556
uniprot
proteins
pubmed
17567961
uniprot
proteins
pubmed
17689225
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18780401
uniprot
proteins
pubmed
1903064
uniprot
proteins
pubmed
19137541
uniprot
proteins
pubmed
19139490
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
1924317
uniprot
proteins
pubmed
19535339
uniprot
proteins
pubmed
1974459
uniprot
proteins
pubmed
19838169
uniprot
proteins
pubmed
19996109
uniprot
proteins
pubmed
20068069
uniprot
proteins
pubmed
21505792
uniprot
proteins
pubmed
21567405
uniprot
proteins
pubmed
22689054
uniprot
proteins
pubmed
2387851
uniprot
proteins
pubmed
24073260
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24381170
uniprot
proteins
pubmed
25402950
uniprot
proteins
pubmed
2601725
uniprot
proteins
pubmed
2721499
uniprot
proteins
pubmed
2780565
uniprot
proteins
pubmed
3154963
uniprot
proteins
pubmed
34667172
uniprot
proteins
pubmed
8181474
uniprot
proteins
pubmed
8292612
uniprot
proteins
pubmed
8328966
uniprot
proteins
pubmed
8555189
uniprot
proteins
pubmed
9200695
uniprot
proteins
pubmed
9336835
uniprot
proteins
sequence_length
449
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Secreted {ECO:0000269|PubMed:11123922, ECO:0000269|PubMed:17260971, ECO:0000269|PubMed:17412999, ECO:0000269|PubMed:17451556, ECO:0000269|PubMed:2387851, ECO:0000269|PubMed:24073260, ECO:0000269|PubMed:2780565, ECO:0000269|PubMed:3154963, ECO:0000269|PubMed:8292612, ECO:0000269|PubMed:8328966}. Note=Can retrotranslocate from the secretory compartments to the cytosol upon cellular stress. {ECO:0000269|PubMed:17451556}.; SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm {ECO:0000269|PubMed:24073260}. Note=Keeps cytoplasmic localization in stressed and unstressed cell. {ECO:0000269|PubMed:24073260}.; SUBCELLULAR LOCATION: [Isoform 6]: Cytoplasm {ECO:0000269|PubMed:24073260}. Note=Keeps cytoplasmic localization in stressed and unstressed cell. {ECO:0000269|PubMed:24073260}.; SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12551933, ECO:0000269|PubMed:19137541}. Cytoplasm {ECO:0000269|PubMed:12551933, ECO:0000269|PubMed:17689225, ECO:0000269|PubMed:19137541, ECO:0000269|PubMed:20068069, ECO:0000269|PubMed:22689054, ECO:0000269|PubMed:24073260}. Mitochondrion membrane; Peripheral membrane protein; Cytoplasmic side {ECO:0000269|PubMed:17689225}. Cytoplasm, cytosol {ECO:0000269|PubMed:17451556, ECO:0000269|PubMed:22689054, ECO:0000269|PubMed:24073260}. Microsome {ECO:0000269|PubMed:22689054}. Endoplasmic reticulum {ECO:0000269|PubMed:16113678, ECO:0000269|PubMed:22689054}. Mitochondrion {ECO:0000269|PubMed:16113678, ECO:0000269|PubMed:22689054}. Mitochondrion membrane {ECO:0000269|PubMed:16113678, ECO:0000269|PubMed:17689225}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:P05371}. Cytoplasmic vesicle, secretory vesicle, chromaffin granule {ECO:0000250}. Note=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). {ECO:0000269|PubMed:12551933, ECO:0000269|PubMed:17451556, ECO:0000269|PubMed:17689225, ECO:0000269|PubMed:20068069, ECO:0000269|PubMed:22689054, ECO:0000269|PubMed:24073260}.
uniprot
proteins