Browse CLU

Summary
SymbolCLU
Nameclusterin
Aliases SGP-2; SP-40; TRPM-2; KUB1; CLU2; complement lysis inhibitor; sulfated glycoprotein 2; testosterone-represse ......
Chromosomal Location8p21-p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Isoform 1: Secreted. Note=Can retrotranslocate from the secretory compartments to the cytosol upon cellular stress.; SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Mitochondrion membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm, cytosol. Microsome. Endoplasmic reticulum. Cytoplasmic vesicle, secretory vesicle, chromaffin granule Note=Isoforms lacking the N-terminal signal sequence have been shown to be cytoplasmic and/or nuclear. Secreted isoforms can retrotranslocate from the secretory compartments to the cytosol upon cellular stress. Detected in perinuclear foci that may be aggresomes containing misfolded, ubiquitinated proteins. Detected at the mitochondrion membrane upon induction of apoptosis.
Domain PF01093 Clusterin
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.

> Gene Ontology
 
Biological Process GO:0001774 microglial cell activation
GO:0001819 positive regulation of cytokine production
GO:0001836 release of cytochrome c from mitochondria
GO:0002250 adaptive immune response
GO:0002274 myeloid leukocyte activation
GO:0002443 leukocyte mediated immunity
GO:0002449 lymphocyte mediated immunity
GO:0002455 humoral immune response mediated by circulating immunoglobulin
GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002576 platelet degranulation
GO:0006457 protein folding
GO:0006809 nitric oxide biosynthetic process
GO:0006869 lipid transport
GO:0006887 exocytosis
GO:0006956 complement activation
GO:0006958 complement activation, classical pathway
GO:0006959 humoral immune response
GO:0007009 plasma membrane organization
GO:0007272 ensheathment of neurons
GO:0008366 axon ensheathment
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
GO:0008637 apoptotic mitochondrial changes
GO:0009615 response to virus
GO:0009894 regulation of catabolic process
GO:0009896 positive regulation of catabolic process
GO:0010001 glial cell differentiation
GO:0010498 proteasomal protein catabolic process
GO:0010876 lipid localization
GO:0014003 oligodendrocyte development
GO:0014009 glial cell proliferation
GO:0015850 organic hydroxy compound transport
GO:0015918 sterol transport
GO:0016064 immunoglobulin mediated immune response
GO:0017038 protein import
GO:0019724 B cell mediated immunity
GO:0021782 glial cell development
GO:0022010 central nervous system myelination
GO:0023041 neuronal signal transduction
GO:0030301 cholesterol transport
GO:0031329 regulation of cellular catabolic process
GO:0031331 positive regulation of cellular catabolic process
GO:0031333 negative regulation of protein complex assembly
GO:0031396 regulation of protein ubiquitination
GO:0031398 positive regulation of protein ubiquitination
GO:0031647 regulation of protein stability
GO:0032286 central nervous system myelin maintenance
GO:0032291 axon ensheathment in central nervous system
GO:0032434 regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032459 regulation of protein oligomerization
GO:0032460 negative regulation of protein oligomerization
GO:0032462 regulation of protein homooligomerization
GO:0032463 negative regulation of protein homooligomerization
GO:0032640 tumor necrosis factor production
GO:0032680 regulation of tumor necrosis factor production
GO:0032760 positive regulation of tumor necrosis factor production
GO:0033674 positive regulation of kinase activity
GO:0034205 beta-amyloid formation
GO:0034248 regulation of cellular amide metabolic process
GO:0034249 negative regulation of cellular amide metabolic process
GO:0034250 positive regulation of cellular amide metabolic process
GO:0035966 response to topologically incorrect protein
GO:0042063 gliogenesis
GO:0042116 macrophage activation
GO:0042176 regulation of protein catabolic process
GO:0042552 myelination
GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0042982 amyloid precursor protein metabolic process
GO:0042987 amyloid precursor protein catabolic process
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0043217 myelin maintenance
GO:0043254 regulation of protein complex assembly
GO:0043691 reverse cholesterol transport
GO:0044089 positive regulation of cellular component biogenesis
GO:0045055 regulated exocytosis
GO:0045428 regulation of nitric oxide biosynthetic process
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045732 positive regulation of protein catabolic process
GO:0045860 positive regulation of protein kinase activity
GO:0045862 positive regulation of proteolysis
GO:0046209 nitric oxide metabolic process
GO:0048709 oligodendrocyte differentiation
GO:0050435 beta-amyloid metabolic process
GO:0050821 protein stabilization
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051131 chaperone-mediated protein complex assembly
GO:0051259 protein oligomerization
GO:0051260 protein homooligomerization
GO:0051788 response to misfolded protein
GO:0061077 chaperone-mediated protein folding
GO:0061136 regulation of proteasomal protein catabolic process
GO:0061517 macrophage proliferation
GO:0061518 microglial cell proliferation
GO:0070661 leukocyte proliferation
GO:0070841 inclusion body assembly
GO:0070997 neuron death
GO:0071706 tumor necrosis factor superfamily cytokine production
GO:0072376 protein activation cascade
GO:0072593 reactive oxygen species metabolic process
GO:0090083 regulation of inclusion body assembly
GO:0090261 positive regulation of inclusion body assembly
GO:0097193 intrinsic apoptotic signaling pathway
GO:0097242 beta-amyloid clearance
GO:1900221 regulation of beta-amyloid clearance
GO:1901214 regulation of neuron death
GO:1901216 positive regulation of neuron death
GO:1901800 positive regulation of proteasomal protein catabolic process
GO:1902003 regulation of beta-amyloid formation
GO:1902004 positive regulation of beta-amyloid formation
GO:1902229 regulation of intrinsic apoptotic signaling pathway in response to DNA damage
GO:1902230 negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage
GO:1902430 negative regulation of beta-amyloid formation
GO:1902532 negative regulation of intracellular signal transduction
GO:1902847 regulation of neuronal signal transduction
GO:1902947 regulation of tau-protein kinase activity
GO:1902949 positive regulation of tau-protein kinase activity
GO:1902988 neurofibrillary tangle assembly
GO:1902991 regulation of amyloid precursor protein catabolic process
GO:1902992 negative regulation of amyloid precursor protein catabolic process
GO:1902993 positive regulation of amyloid precursor protein catabolic process
GO:1902996 regulation of neurofibrillary tangle assembly
GO:1902998 positive regulation of neurofibrillary tangle assembly
GO:1903050 regulation of proteolysis involved in cellular protein catabolic process
GO:1903052 positive regulation of proteolysis involved in cellular protein catabolic process
GO:1903320 regulation of protein modification by small protein conjugation or removal
GO:1903322 positive regulation of protein modification by small protein conjugation or removal
GO:1903362 regulation of cellular protein catabolic process
GO:1903364 positive regulation of cellular protein catabolic process
GO:1903409 reactive oxygen species biosynthetic process
GO:1903426 regulation of reactive oxygen species biosynthetic process
GO:1903428 positive regulation of reactive oxygen species biosynthetic process
GO:1903555 regulation of tumor necrosis factor superfamily cytokine production
GO:1903557 positive regulation of tumor necrosis factor superfamily cytokine production
GO:1904407 positive regulation of nitric oxide metabolic process
GO:2000058 regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:2000060 positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:2000377 regulation of reactive oxygen species metabolic process
GO:2000379 positive regulation of reactive oxygen species metabolic process
GO:2001020 regulation of response to DNA damage stimulus
GO:2001021 negative regulation of response to DNA damage stimulus
GO:2001057 reactive nitrogen species metabolic process
GO:2001233 regulation of apoptotic signaling pathway
GO:2001234 negative regulation of apoptotic signaling pathway
GO:2001242 regulation of intrinsic apoptotic signaling pathway
GO:2001243 negative regulation of intrinsic apoptotic signaling pathway
Molecular Function GO:0031625 ubiquitin protein ligase binding
GO:0044389 ubiquitin-like protein ligase binding
GO:0051087 chaperone binding
GO:0051787 misfolded protein binding
Cellular Component GO:0016234 inclusion body
GO:0030141 secretory granule
GO:0030425 dendrite
GO:0031091 platelet alpha granule
GO:0031093 platelet alpha granule lumen
GO:0031983 vesicle lumen
GO:0032994 protein-lipid complex
GO:0034358 plasma lipoprotein particle
GO:0034364 high-density lipoprotein particle
GO:0034366 spherical high-density lipoprotein particle
GO:0034774 secretory granule lumen
GO:0042583 chromaffin granule
GO:0060205 cytoplasmic membrane-bounded vesicle lumen
GO:0072562 blood microparticle
GO:0097418 neurofibrillary tangle
GO:0097440 apical dendrite
GO:0099503 secretory vesicle
GO:1990777 lipoprotein particle
> KEGG and Reactome Pathway
 
KEGG hsa04610 Complement and coagulation cascades
Reactome R-HSA-6803157: Antimicrobial peptides
R-HSA-166658: Complement cascade
R-HSA-109582: Hemostasis
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-114608: Platelet degranulation
R-HSA-76005: Response to elevated platelet cytosolic Ca2+
R-HSA-166665: Terminal pathway of complement
Summary
SymbolCLU
Nameclusterin
Aliases SGP-2; SP-40; TRPM-2; KUB1; CLU2; complement lysis inhibitor; sulfated glycoprotein 2; testosterone-represse ......
Chromosomal Location8p21-p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between CLU and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 

There is no record.
Summary
SymbolCLU
Nameclusterin
Aliases SGP-2; SP-40; TRPM-2; KUB1; CLU2; complement lysis inhibitor; sulfated glycoprotein 2; testosterone-represse ......
Chromosomal Location8p21-p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of CLU in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolCLU
Nameclusterin
Aliases SGP-2; SP-40; TRPM-2; KUB1; CLU2; complement lysis inhibitor; sulfated glycoprotein 2; testosterone-represse ......
Chromosomal Location8p21-p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of CLU in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.2590.785
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.5560.818
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.8620.63
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.1110.884
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.2630.926
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.5750.863
729033130MelanomaallAnti-PD-1 (nivolumab) 26231.0530.183
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15111.7480.303
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.070.974
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.740.837
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 28-0.8910.868
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.640.00343
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of CLU in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277304.1-4.10.561
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275905.1-5.10.549
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.85.9-1.11
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.79.1-1.41
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolCLU
Nameclusterin
Aliases SGP-2; SP-40; TRPM-2; KUB1; CLU2; complement lysis inhibitor; sulfated glycoprotein 2; testosterone-represse ......
Chromosomal Location8p21-p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CLU. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolCLU
Nameclusterin
Aliases SGP-2; SP-40; TRPM-2; KUB1; CLU2; complement lysis inhibitor; sulfated glycoprotein 2; testosterone-represse ......
Chromosomal Location8p21-p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CLU. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CLU.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCLU
Nameclusterin
Aliases SGP-2; SP-40; TRPM-2; KUB1; CLU2; complement lysis inhibitor; sulfated glycoprotein 2; testosterone-represse ......
Chromosomal Location8p21-p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CLU. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolCLU
Nameclusterin
Aliases SGP-2; SP-40; TRPM-2; KUB1; CLU2; complement lysis inhibitor; sulfated glycoprotein 2; testosterone-represse ......
Chromosomal Location8p21-p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CLU expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCLU
Nameclusterin
Aliases SGP-2; SP-40; TRPM-2; KUB1; CLU2; complement lysis inhibitor; sulfated glycoprotein 2; testosterone-represse ......
Chromosomal Location8p21-p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CLU and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCLU
Nameclusterin
Aliases SGP-2; SP-40; TRPM-2; KUB1; CLU2; complement lysis inhibitor; sulfated glycoprotein 2; testosterone-represse ......
Chromosomal Location8p21-p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CLU collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting CLU.
ID Name Drug Type Targets #Targets
DB01593ZincSmall MoleculeA1BG, A2M, AGT, AHSG, ALDOA, APCS, APLP1, APLP2, APOA1, APOA2, APO ......119
DB09130CopperSmall MoleculeA1BG, ACTG1, ACTN1, ACY1, AFM, AGT, AHCY, AHSG, AKR1A1, ANXA4, ANX ......141