Tbio CLU Clusterin

Protein Summary

Description

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. The protein encoded by this gene is a secreted chaperone that can under some stress conditions also be found in the cell cytosol. It has been suggested to be involved in several basic biological events such as cell death, tumor progression, and neurodegenerative disorders. Alternate splicing results in both coding and non-coding variants.[provided by RefSeq, May 2011]

Uniprot Accession IDs

• P10909
• B2R9Q1
• B3KSE6
• P11380
• P11381
• Q2TU75
• Q5HYC1
• Q7Z5B9

Gene Name

• CLU

Ensembl ID

• ENST00000316403
• ENSP00000315130
• ENSG00000120885
• ENST00000405140
• ENSP00000385419
• ENST00000523500
• ENSP00000429620

Symbol

• APOJ
• CLI
• KUB1
• CLI
• AAG4
• APOJ
• CLU1
• CLU2
• KUB1
• SGP2
• APO-J
• SGP-2
• SP-40
• TRPM2
• TRPM-2
• NA1/NA2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
transcription factor perturbation	1
virus perturbation	0.96
PubMedID	0.95
chemical	0.87

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2031.24   (req: < 5)

Gene RIFs: 385   (req: <= 3)

Antibodies: 1092   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2031.24   (req: >= 5)

Gene RIFs: 385   (req: > 3)

Antibodies: 1092   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 57

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

tutorial

No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (321)

Explore Interacting Targets

1 – 10 of 321

• See Interactions on String-DB

SDK2

Tdark

Novelty:  0.08867136

p_int:  0.999979449

p_ni:  0.000020551

Score:  0.202

Data Source:  BioPlex,STRINGDB

ATP2B2

Tbio

Family:  Transporter

Novelty:  0.007782

p_int:  0.999913591

p_ni:  0.000086409

Score:  0.204

Data Source:  BioPlex,STRINGDB

PTPRS

Tchem

Family:  Enzyme

Novelty:  0.00587115

p_int:  0.999888761

p_ni:  0.000111239

Score:  0.17

Data Source:  BioPlex,STRINGDB

TENM3

Tbio

Novelty:  0.0251948

p_int:  0.999738844

p_ni:  0.000261155

p_wrong:  1e-9

Score:  0.359

Data Source:  BioPlex,STRINGDB

FAT4

Tbio

Novelty:  0.01739918

p_int:  0.999655832

p_ni:  0.000344168

Data Source:  BioPlex

FBXO27

Tdark

Novelty:  0.27910336

p_int:  0.999641451

p_ni:  0.000008264

p_wrong:  0.000350285

Score:  0.187

Data Source:  BioPlex,STRINGDB

CBWD3

Tdark

Novelty:  0.03639787

p_int:  0.99948875

p_ni:  0.000511242

p_wrong:  9e-9

Data Source:  BioPlex

KIAA0355

Tdark

Novelty:  0.97113831

p_int:  0.999447195

p_ni:  0.000552805

Score:  0.185

Data Source:  BioPlex,STRINGDB

DHX57

Tdark

Family:  Enzyme

Novelty:  0.8244078

p_int:  0.998109936

p_ni:  0.001890064

Data Source:  BioPlex

ITGA8

Tbio

Novelty:  0.0220023

p_int:  0.997451574

p_ni:  0.00254841

p_wrong:  1.6e-8

Data Source:  BioPlex

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (20)

Reactome (10)

KEGG (1)

PathwayCommons (2)

WikiPathways (7)

Antimicrobial peptides (R-HSA-6803157)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Antimicrobial peptides	89 targets	R-HSA-6803157
Reactome	Complement cascade	133 targets	R-HSA-166658
Reactome	Hemostasis	666 targets	R-HSA-109582
Reactome	Immune System	2246 targets	R-HSA-168256
Reactome	Innate Immune System	1188 targets	R-HSA-168249

Name	Explore in Pharos	Explore in Source
Antimicrobial peptides	89 targets	R-HSA-6803157
Complement cascade	133 targets	R-HSA-166658
Hemostasis	666 targets	R-HSA-109582
Immune System	2246 targets	R-HSA-168256
Innate Immune System	1188 targets	R-HSA-168249

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (79)

Functions (8)

Components (22)

Processes (49)

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1 – 8 of 8

GO Term	Evidence	Assigned by
amyloid-beta binding	Inferred from Direct Assay (IDA)	ARUK-UCL
misfolded protein binding	Inferred from Direct Assay (IDA)	UniProtKB
ubiquitin protein ligase binding	Inferred from Direct Assay (IDA)	UniProtKB
low-density lipoprotein particle receptor binding	Inferred from Physical Interaction (IPI)	ARUK-UCL
protein-containing complex binding	Inferred from Physical Interaction (IPI)	ARUK-UCL
tau protein binding	Inferred from Physical Interaction (IPI)	ARUK-UCL
chaperone binding	Inferred from Sequence or structural Similarity (ISS)	ParkinsonsUK-UCL
protein heterodimerization activity	Traceable Author Statement (TAS)	ARUK-UCL

Disease Associations (null)

No disease associations found

GWAS Traits (20)

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 5 of 20

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
smoking status measurement	EFO_0006527	2	2	3		93.4
smoking initiation	EFO_0005670	3	3	3		93
Alzheimer's disease	EFO_0000249	6	3	0	4.8	89.5
family history of Alzheimer’s disease	EFO_0009268	1	2	0	8.7	83.2
cigarettes per day measurement	EFO_0006525	3	3	4		75.2

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
smoking status measurement	EFO_0006527	3		93.4
smoking initiation	EFO_0005670	3		93
Alzheimer's disease	EFO_0000249	0	4.8	89.5
family history of Alzheimer’s disease	EFO_0009268	0	8.7	83.2
cigarettes per day measurement	EFO_0006525	4		75.2

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UniProt Keyword Find Similar Targets

No Header	No Header
Alternative splicing
Apoptosis
Chaperone
Complement pathway
Complete proteome
Cytoplasm
Cytoplasmic vesicle
Direct protein sequencing
Disulfide bond
Endoplasmic reticulum

GWAS Trait Find Similar Targets

No Header	No Header
age at onset
Alzheimer's disease
anorexia nervosa
autism spectrum disorder
bipolar disorder
body height
cannabis dependence
cigarettes per day measurement
family history of Alzheimer’s disease
late-onset Alzheimers disease

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cardiovascular system phenotype
homeostasis/metabolism phenotype
immune system phenotype
muscle phenotype
renal/urinary system phenotype

IDG Resources

No IDG generated resources found

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	clusterin	VGNC:908	464075
Macaque	clusterin		677866
Mouse	clusterin	MGI:88423	12759
Rat	clusterin	RGD:3907	24854
Dog	clusterin	VGNC:39369	442971

Species	Name	OMA	EggNOG	Inparanoid
Chimp	clusterin
Macaque	clusterin
Mouse	clusterin
Rat	clusterin
Dog	clusterin

Publication Statistics

PubMed Score 2031.24

PubMed score by year

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PubTator Score 901.05

PubTator score by year

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Related Publications

Text Mined References (472)

GeneRif Annotations (385)

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PMID	Year	Title