CLU - Clusterin - human protein (Function)
 
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CLU »  Clusterin
 
Protein also known as:  Testosterone-repressed prostate message 2 (TRPM-2). Cleaved into:  Clusterin alpha chain; Clusterin beta chain.
Gene name:  CLU
Family name: Clusterin
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 264 5
GENE REF ISO

Function

 show evidences
Overview 
Isoforms  Iso 1 and Iso 2   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.  
15
  • CuratedUniProtKB
GO molecular function 
Not  ATPase activitydefinition[GO:0016887]  
1
  • IDAUniProtKB
Misfolded protein bindingdefinition[GO:0051787]  
2
  • IPIBHF-UCL
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
4
  • IPIIntAct
  • IPIBHF-UCL
Ubiquitin protein ligase bindingdefinition[GO:0031625]  
1
  • IDAUniProtKB
GO biological process 
Chaperone-mediated protein foldingdefinition[GO:0061077]  
1
  • IDAUniProtKB
Complement activationdefinition[GO:0006956]  
1
  • TASPINC
Complement activation, classical pathwaydefinition[GO:0006958]  
  • IEAUniProtKB KW
Innate immune responsedefinition[GO:0045087]  
  • IEAUniProtKB KW
Isoform  Iso 4   Intrinsic apoptotic signaling pathwaydefinition[GO:0097193]  
1
  • IDAUniProtKB
Lipid metabolic processdefinition[GO:0006629]  
1
  • NASPINC
Negative regulation of intrinsic apoptotic signaling pathway in response to DNA damagedefinition[GO:1902230]  
1
  • IMPBHF-UCL
Negative regulation of protein homooligomerizationdefinition[GO:0032463]  
1
  • IMPBHF-UCL
Isoform  Iso 4   Positive regulation of apoptotic processdefinition[GO:0043065]  
1
  • IMPUniProtKB
Isoform  Iso 4   Positive regulation of intrinsic apoptotic signaling pathwaydefinition[GO:2001244]  
1
  • IMPUniProtKB
Positive regulation of NF-kappaB transcription factor activitydefinition[GO:0051092]  
1
  • IMPUniProtKB
Positive regulation of proteasomal ubiquitin-dependent protein catabolic processdefinition[GO:0032436]  
1
  • IMPUniProtKB
Positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic processdefinition[GO:2000060]  
1
  • IMPUniProtKB
Protein stabilizationdefinition[GO:0050821]  
1
  • IDAUniProtKB
Release of cytochrome c from mitochondriadefinition[GO:0001836]  
1
  • ICBHF-UCL
Response to misfolded proteindefinition[GO:0051788]  
1
  • IDABHF-UCL
Response to virusdefinition[GO:0009615]  
1
  • IEPUniProtKB
Reverse cholesterol transportdefinition[GO:0043691]  
1
  • TASBHF-UCL
Pathways 
According to Reactome, this protein belongs to the following pathway:
Hemostasis  REACT_604  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Complement pathway  definition   [KW-0180]
Immunity  definition   [KW-0391]
Innate immunity  definition   [KW-0399]
Molecular function 
Chaperone  definition   [KW-0143]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: Clusterin
GenomeRNAi: 1191
PRO: PR:P10909