Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTRL76H)

DTT Name Clusterin messenger RNA (Clusterin mRNA)
Synonyms
Testosteronerepressed prostate message 2 (mRNA); Testosterone-repressed prostate message 2 (mRNA); TRPM-2 (mRNA); NA1/NA2 (mRNA); Ku70binding protein 1 (mRNA); Ku70-binding protein 1 (mRNA); KUB1 (mRNA); Complementassociated protein SP40,40 (mRNA); Complement-associated protein SP-40,40 (mRNA); Complement cytolysis inhibitor (mRNA); Clusterin alpha chain (mRNA); Clusterin (mRNA); CLI (mRNA); Apolipoprotein J (mRNA); ApoJ (mRNA); Apo-J (mRNA); Agingassociated gene 4 protein (mRNA); Aging-associated gene 4 protein (mRNA); AAG4 (mRNA)
Gene Name CLU
DTT Type
Clinical trial target
 [1]
BioChemical Class
mRNA target
UniProt ID
CLUS_HUMAN
TTD ID
T95899
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
Platelet degranulation (R-HSA-114608 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Custirsen DMIQ31Y Breast cancer 2C60-2C65 Phase 3 [1]
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Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Prostate cancer 2C82 Prostate 1.52E-04 -0.66 -0.65
Lung cancer 2C82 Lung tissue 2.38E-99 -1.66 -2.67
Breast cancer 2C82 Breast tissue 7.23E-111 -1.48 -2.11
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References

1 Over-expression of clusterin is a resistance factor to the anti-cancer effect of histone deacetylase inhibitors. Eur J Cancer. 2009 Jul;45(10):1846-54.