General Information of Drug Therapeutic Target (DTT) (ID: TTN8T0E)

DTT Name Clusterin (CLU)
Synonyms
Testosteronerepressed prostate message 2; Testosterone-repressed prostate message 2; TRPM-2; NA1/NA2; Ku70binding protein 1; Ku70-binding protein 1; KUB1; Complementassociated protein SP40,40; Complement-associated protein SP-40,40; Complement cytolysis inhibitor; Clusterin alpha chain; CLI; Apolipoprotein J; ApoJ; Apo-J; Agingassociated gene 4 protein; Aging-associated gene 4 protein; AAG4
Gene Name CLU
DTT Type
Literature-reported target
[1]
UniProt ID
CLUS_HUMAN
TTD ID
T96669
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MMKTLLLFVGLLLTWESGQVLGDQTVSDNELQEMSNQGSKYVNKEIQNAVNGVKQIKTLI
EKTNEERKTLLSNLEEAKKKKEDALNETRESETKLKELPGVCNETMMALWEECKPCLKQT
CMKFYARVCRSGSGLVGRQLEEFLNQSSPFYFWMNGDRIDSLLENDRQQTHMLDVMQDHF
SRASSIIDELFQDRFFTREPQDTYHYLPFSLPHRRPHFFFPKSRIVRSLMPFSPYEPLNF
HAMFQPFLEMIHEAQQAMDIHFHSPAFQHPPTEFIREGDDDRTVCREIRHNSTGCLRMKD
QCDKCREILSVDCSTNNPSQAKLRRELDESLQVAERLTRKYNELLKSYQWKMLNTSSLLE
QLNEQFNWVSRLANLTQGEDQYYLRVTTVASHTSDSDVPSGVTEVVVKLFDSDPITVTVP
VEVSRKNPKFMETVAEKALQEYRKKHREE
Function
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. Isoform 1 functions as extracellular chaperone that prevents aggregation of nonnative proteins.
KEGG Pathway
Complement and coagulation cascades (hsa04610 )
Reactome Pathway
Terminal pathway of complement (R-HSA-166665 )
Antimicrobial peptides (R-HSA-6803157 )
Regulation of Complement cascade (R-HSA-977606 )
Platelet degranulation (R-HSA-114608 )

References

1 Clusterin is a gene-specific target of microRNA-21 in head and neck squamous cell carcinoma. Clin Cancer Res. 2014 Feb 15;20(4):868-77.