Clusterin (P10909)

Uniprot ID P10909
Protein Name Clusterin
Gene Name CLU
Species Homo sapiens (Human)
Signal peptide(a) Y Secretome P(b) 0.848
Function Isoform 1 functions 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. 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. .
GO - Molecular function
  • amyloid-beta binding : IDA:ARUK-UCL
  • chaperone binding : ISS:ParkinsonsUK-UCL
  • low-density lipoprotein particle receptor binding : IPI:ARUK-UCL
  • misfolded protein binding : IDA:UniProtKB
  • protein heterodimerization activity : TAS:ARUK-UCL
  • protein-containing complex binding : IPI:ARUK-UCL
  • tau protein binding : IPI:ARUK-UCL
  • ubiquitin protein ligase binding : IDA:UniProtKB
GO - Biological process
  • antimicrobial humoral response : TAS:Reactome
  • cell morphogenesis : IDA:Alzheimers_University_of_Toronto
  • central nervous system myelin maintenance : IMP:Alzheimers_University_of_Toronto
  • chaperone-mediated protein complex assembly : IDA:Alzheimers_University_of_Toronto
  • chaperone-mediated protein folding : IDA:UniProtKB
  • chaperone-mediated protein transport involved in chaperone-mediated autophagy : IC:ARUK-UCL
  • complement activation : TAS:ProtInc
  • complement activation, classical pathway : IEA:UniProtKB-KW
  • innate immune response : IEA:UniProtKB-KW
  • intrinsic apoptotic signaling pathway : IDA:UniProtKB
  • lipid metabolic process : NAS:ProtInc
  • microglial cell activation : IDA:Alzheimers_University_of_Toronto
  • microglial cell proliferation : IDA:Alzheimers_University_of_Toronto
  • negative regulation of amyloid fibril formation : IDA:ARUK-UCL
  • negative regulation of amyloid-beta formation : IDA:Alzheimers_University_of_Toronto
  • negative regulation of cell death : IMP:ARUK-UCL
  • negative regulation of cellular response to thapsigargin : IMP:ARUK-UCL
  • negative regulation of cellular response to tunicamycin : IMP:ARUK-UCL
  • negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage : IMP:BHF-UCL
  • negative regulation of protein homooligomerization : IDA:ARUK-UCL
  • negative regulation of release of cytochrome c from mitochondria : TAS:ARUK-UCL
  • negative regulation of response to endoplasmic reticulum stress : IMP:ARUK-UCL
  • platelet degranulation : TAS:Reactome
  • positive regulation of amyloid fibril formation : TAS:ARUK-UCL
  • positive regulation of amyloid-beta formation : ISS:Alzheimers_University_of_Toronto
  • positive regulation of apoptotic process : IMP:UniProtKB
  • positive regulation of gene expression : ISS:ARUK-UCL
  • positive regulation of intrinsic apoptotic signaling pathway : IMP:UniProtKB
  • positive regulation of neurofibrillary tangle assembly : IMP:Alzheimers_University_of_Toronto
  • positive regulation of neuron death : IDA:Alzheimers_University_of_Toronto
  • positive regulation of NF-kappaB transcription factor activity : IMP:UniProtKB
  • positive regulation of nitric oxide biosynthetic process : IDA:Alzheimers_University_of_Toronto
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process : IMP:UniProtKB
  • positive regulation of protein homooligomerization : IDA:ARUK-UCL
  • positive regulation of receptor-mediated endocytosis : IGI:ARUK-UCL
  • positive regulation of tau-protein kinase activity : IMP:Alzheimers_University_of_Toronto
  • positive regulation of tumor necrosis factor production : IDA:Alzheimers_University_of_Toronto
  • positive regulation of ubiquitin-dependent protein catabolic process : IMP:UniProtKB
  • protein import : IDA:Alzheimers_University_of_Toronto
  • protein stabilization : IDA:UniProtKB
  • protein targeting to lysosome involved in chaperone-mediated autophagy : IC:ARUK-UCL
  • regulation of amyloid-beta clearance : IDA:Alzheimers_University_of_Toronto
  • regulation of complement activation : TAS:Reactome
  • regulation of neuron death : IDA:Alzheimers_University_of_Toronto
  • regulation of neuronal signal transduction : IMP:Alzheimers_University_of_Toronto
  • release of cytochrome c from mitochondria : IC:BHF-UCL
  • response to misfolded protein : IDA:BHF-UCL
  • response to virus : IEP:UniProtKB
  • reverse cholesterol transport : TAS:BHF-UCL
Back
(a) The Signal peptide D-score cutoff for "YES"(having signal peptide) is 0.45.
(b) Non-classically secreted proteins should obtain an NN-score(Neural Networks score) exceeding the normal threshold of 0.5, but not at the same time be predicted to contain a signal peptide.