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CLU clusterin [ Homo sapiens (human) ]

Gene ID: 1191, updated on 19-Aug-2018

Summary

Official Symbol
CLUprovided by HGNC
Official Full Name
clusterinprovided by HGNC
Primary source
HGNC:HGNC:2095
See related
Ensembl:ENSG00000120885 MIM:185430; Vega:OTTHUMG00000102114
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CLI; AAG4; APOJ; CLU1; CLU2; KUB1; SGP2; APO-J; SGP-2; SP-40; TRPM2; TRPM-2; NA1/NA2
Summary
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]
Expression
Broad expression in brain (RPKM 523.1), liver (RPKM 432.6) and 16 other tissues See more
Orthologs

Genomic context

See CLU in Genome Data Viewer
Location:
8p21.1
Exon count:
11
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 8 NC_000008.11 (27596917..27615031, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (27454434..27472328, complement)

Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene cholinergic receptor nicotinic alpha 2 subunit Neighboring gene epoxide hydrolase 2 Neighboring gene gulonolactone (L-) oxidase, pseudogene Neighboring gene microRNA 6843 Neighboring gene scavenger receptor class A member 3 Neighboring gene RNA, U6 small nuclear 1086, pseudogene Neighboring gene microRNA 3622b Neighboring gene microRNA 3622a

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Biological insights from 108 schizophrenia-associated genetic loci.
NHGRI GWA Catalog
Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease.
NHGRI GWA Catalog
Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease.
NHGRI GWA Catalog
Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease.
NHGRI GWA Catalog
Genome-wide association study of panic disorder in the Japanese population.
NHGRI GWA Catalog
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.
NHGRI GWA Catalog
The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease.
NHGRI GWA Catalog

Pathways from BioSystems

  • Antimicrobial peptides, organism-specific biosystem (from REACTOME)
    Antimicrobial peptides, organism-specific biosystemAntimicrobial peptides (AMPs) are small molecular weight proteins with broad spectrum of antimicrobial activity against bacteria, viruses, and fungi (Zasloff M 2002; Radek K & Gallo R 2007). The majo...
  • Complement and Coagulation Cascades, organism-specific biosystem (from WikiPathways)
    Complement and Coagulation Cascades, organism-specific biosystemBlood coagulation is a series of coordinated and calcium-dependent proenzyme-to-serine protease conversions likely to be localized on the surfaces of activated cells in vivo. It culminates in the for...
  • Complement and coagulation cascades, organism-specific biosystem (from KEGG)
    Complement and coagulation cascades, organism-specific biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
  • Complement and coagulation cascades, conserved biosystem (from KEGG)
    Complement and coagulation cascades, conserved biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
  • Complement cascade, organism-specific biosystem (from REACTOME)
    Complement cascade, organism-specific biosystemIn the complement cascade, a panel of soluble molecules rapidly and effectively senses a danger or damage and triggers reactions to provide a response that discriminates among foreign intruders, cell...
  • Hemostasis, organism-specific biosystem (from REACTOME)
    Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
    Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...
  • Platelet degranulation, organism-specific biosystem (from REACTOME)
    Platelet degranulation, organism-specific biosystemPlatelets function as exocytotic cells, secreting a plethora of effector molecules at sites of vascular injury. Platelets contain a number of distinguishable storage granules including alpha granules...
  • Response to elevated platelet cytosolic Ca2+, organism-specific biosystem (from REACTOME)
    Response to elevated platelet cytosolic Ca2+, organism-specific biosystemActivation of phospholipase C enzymes results in the generation of second messengers of the phosphatidylinositol pathway. The events resulting from this pathway are a rise in intracellular calcium an...
  • Terminal pathway of complement, organism-specific biosystem (from REACTOME)
    Terminal pathway of complement, organism-specific biosystemAfter cleavage of C5, C5b undergoes conformational changes and exposes a binding site for C6. C5b6 binds C7 resulting in the exposure of membrane binding sites and incorporation into target membranes...
  • Validated targets of C-MYC transcriptional repression, organism-specific biosystem (from Pathway Interaction Database)
    Validated targets of C-MYC transcriptional repression, organism-specific biosystem
    Validated targets of C-MYC transcriptional repression

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC24903

Gene Ontology Provided by GOA

Function Evidence Code Pubs
NOT ATPase activity IDA
Inferred from Direct Assay
more info
PubMed 
amyloid-beta binding IDA
Inferred from Direct Assay
more info
PubMed 
amyloid-beta binding IPI
Inferred from Physical Interaction
more info
PubMed 
chaperone binding ISS
Inferred from Sequence or Structural Similarity
more info
 
low-density lipoprotein particle receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
misfolded protein binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
misfolded protein binding IDA
Inferred from Direct Assay
more info
PubMed 
misfolded protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein-containing complex binding IPI
Inferred from Physical Interaction
more info
PubMed 
tau protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin protein ligase binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
antimicrobial humoral response TAS
Traceable Author Statement
more info
 
cell morphogenesis IDA
Inferred from Direct Assay
more info
PubMed 
central nervous system myelin maintenance IMP
Inferred from Mutant Phenotype
more info
PubMed 
chaperone-mediated protein complex assembly IDA
Inferred from Direct Assay
more info
PubMed 
chaperone-mediated protein folding IDA
Inferred from Direct Assay
more info
PubMed 
chaperone-mediated protein transport involved in chaperone-mediated autophagy IC
Inferred by Curator
more info
PubMed 
complement activation TAS
Traceable Author Statement
more info
PubMed 
complement activation, classical pathway IEA
Inferred from Electronic Annotation
more info
 
innate immune response IEA
Inferred from Electronic Annotation
more info
 
lipid metabolic process NAS
Non-traceable Author Statement
more info
PubMed 
microglial cell activation IDA
Inferred from Direct Assay
more info
PubMed 
microglial cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of amyloid fibril formation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of amyloid fibril formation TAS
Traceable Author Statement
more info
PubMed 
negative regulation of amyloid-beta formation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cell death IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of cell death TAS
Traceable Author Statement
more info
PubMed 
negative regulation of cellular response to thapsigargin IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of cellular response to tunicamycin IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of protein homooligomerization IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of protein homooligomerization IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of protein homooligomerization IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of release of cytochrome c from mitochondria TAS
Traceable Author Statement
more info
PubMed 
negative regulation of response to endoplasmic reticulum stress IMP
Inferred from Mutant Phenotype
more info
PubMed 
platelet degranulation TAS
Traceable Author Statement
more info
 
positive regulation of NF-kappaB transcription factor activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of amyloid fibril formation TAS
Traceable Author Statement
more info
PubMed 
positive regulation of amyloid-beta formation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of gene expression ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of neurofibrillary tangle assembly IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of neuron death IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of neuron death IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of neuron death ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of nitric oxide biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of proteasomal ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of proteasomal ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of protein homooligomerization IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of receptor-mediated endocytosis IGI
Inferred from Genetic Interaction
more info
PubMed 
positive regulation of tau-protein kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of tumor necrosis factor production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein import IDA
Inferred from Direct Assay
more info
PubMed 
protein stabilization IDA
Inferred from Direct Assay
more info
PubMed 
protein targeting to lysosome involved in chaperone-mediated autophagy IC
Inferred by Curator
more info
PubMed 
regulation of amyloid-beta clearance IDA
Inferred from Direct Assay
more info
PubMed 
regulation of complement activation TAS
Traceable Author Statement
more info
 
regulation of neuron death IDA
Inferred from Direct Assay
more info
PubMed 
regulation of neuron death IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of neuronal signal transduction IMP
Inferred from Mutant Phenotype
more info
PubMed 
release of cytochrome c from mitochondria IC
Inferred by Curator
more info
PubMed 
response to misfolded protein IDA
Inferred from Direct Assay
more info
PubMed 
response to virus IEP
Inferred from Expression Pattern
more info
PubMed 
reverse cholesterol transport TAS
Traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
Golgi apparatus ISS
Inferred from Sequence or Structural Similarity
more info
 
apical dendrite IDA
Inferred from Direct Assay
more info
PubMed 
blood microparticle HDA PubMed 
colocalizes_with cell periphery IDA
Inferred from Direct Assay
more info
PubMed 
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
chromaffin granule IEA
Inferred from Electronic Annotation
more info
 
collagen-containing extracellular matrix HDA PubMed 
colocalizes_with collagen-containing extracellular matrix HDA PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
colocalizes_with cytoskeleton IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IEA
Inferred from Electronic Annotation
more info
 
endoplasmic reticulum IEA
Inferred from Electronic Annotation
more info
 
extracellular exosome HDA PubMed 
extracellular matrix HDA PubMed 
extracellular region HDA PubMed 
extracellular region TAS
Traceable Author Statement
more info
PubMed 
extracellular space HDA PubMed 
extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
extracellular space IDA
Inferred from Direct Assay
more info
PubMed 
intracellular TAS
Traceable Author Statement
more info
PubMed 
colocalizes_with membrane IDA
Inferred from Direct Assay
more info
PubMed 
mitochondrial membrane IEA
Inferred from Electronic Annotation
more info
 
mitochondrion IDA
Inferred from Direct Assay
more info
PubMed 
neurofibrillary tangle IDA
Inferred from Direct Assay
more info
PubMed 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
platelet alpha granule lumen TAS
Traceable Author Statement
more info
 
protein-containing complex IDA
Inferred from Direct Assay
more info
PubMed 
spherical high-density lipoprotein particle IDA
Inferred from Direct Assay
more info
PubMed 
synapse IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
clusterin
Names
aging-associated protein 4
apolipoprotein J
complement cytolysis inhibitor
complement lysis inhibitor
complement-associated protein SP-40,40
ku70-binding protein 1
sulfated glycoprotein 2
testosterone-repressed prostate message 2

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_027845.1 RefSeqGene

    Range
    5000..22894
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001831.3NP_001822.3  clusterin preproprotein

    See identical proteins and their annotated locations for NP_001822.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the functional protein.
    Source sequence(s)
    AF311103, BC010514, BM682289, DN990822
    Consensus CDS
    CCDS47832.1
    UniProtKB/Swiss-Prot
    P10909
    Related
    ENSP00000315130.10, OTTHUMP00000128311, ENST00000316403.14, OTTHUMT00000219953
    Conserved Domains (1) summary
    pfam01093
    Location:30445
    Clusterin; Clusterin

RNA

  1. NR_038335.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) has an alternate 5' exon, compared to variant 1. This variant is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with translation of the longest ORF; translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AF311103, BM682289, M25915
  2. NR_045494.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) has an alternate 5' exon, compared to variant 1. This variant is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with translation of the longest ORF; translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AF311103, BC019588, BM682289, BP193735, EB385800

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000008.11 Reference GRCh38.p12 Primary Assembly

    Range
    27596917..27615031 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006716284.3XP_006716347.1  clusterin isoform X1

    See identical proteins and their annotated locations for XP_006716347.1

    UniProtKB/Swiss-Prot
    P10909
    Conserved Domains (3) summary
    smart00030
    Location:75279
    CLb; CLUSTERIN Beta chain
    smart00035
    Location:280495
    CLa; CLUSTERIN alpha chain
    pfam01093
    Location:82497
    Clusterin; Clusterin
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