Human Gene CLU (ENST00000316403.15) from GENCODE V44
  Description: Homo sapiens clusterin (CLU), transcript variant 4, non-coding RNA. (from RefSeq NR_045494)
RefSeq Summary (NM_001831): 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].
Gencode Transcript: ENST00000316403.15
Gencode Gene: ENSG00000120885.22
Transcript (Including UTRs)
   Position: hg38 chr8:27,596,917-27,614,700 Size: 17,784 Total Exon Count: 9 Strand: -
Coding Region
   Position: hg38 chr8:27,598,241-27,610,571 Size: 12,331 Coding Exon Count: 8 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr8:27,596,917-27,614,700)mRNA (may differ from genome)Protein (449 aa)
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HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: CLUS_HUMAN
DESCRIPTION: RecName: Full=Clusterin; AltName: Full=Aging-associated gene 4 protein; AltName: Full=Apolipoprotein J; Short=Apo-J; AltName: Full=Complement cytolysis inhibitor; Short=CLI; AltName: Full=Complement-associated protein SP-40,40; AltName: Full=Ku70-binding protein 1; AltName: Full=NA1/NA2; AltName: Full=Testosterone-repressed prostate message 2; Short=TRPM-2; Contains: RecName: Full=Clusterin beta chain; AltName: Full=ApoJalpha; AltName: Full=Complement cytolysis inhibitor a chain; Contains: RecName: Full=Clusterin alpha chain; AltName: Full=ApoJbeta; AltName: Full=Complement cytolysis inhibitor b chain; Flags: Precursor;
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.
SUBUNIT: Antiparallel disulfide-linked heterodimer of an alpha chain and a beta chain. Self-associates and forms higher oligomers. Interacts with a broad range of misfolded proteins, including APP, APOC2 and LYZ. Slightly acidic pH promotes interaction with misfolded proteins. Forms high-molecular weight oligomers upon interaction with misfolded proteins. Interacts with APOA1, LRP2, CLUAP1 AND PON1. Interacts with the complement complex. Interacts (via alpha chain) with XRCC6. Interacts with SYVN1, COMMD1, BTRC, CUL1 and with ubiquitin and SCF (SKP1-CUL1-F- box protein) E3 ubiquitin-protein ligase complexes. Interacts (via alpha chain) with BAX in stressed cells, where BAX undergoes a conformation change leading to association with the mitochondrial membrane. Does not interact with BAX in unstressed cells. Found in a complex with LTF, CLU, EPPIN and SEMG1.
INTERACTION: Q07817-1:BCL2L1; NbExp=6; IntAct=EBI-4322678, EBI-287195; Q9NRI5:DISC1; NbExp=4; IntAct=EBI-1104674, EBI-529989; P01100:FOS; NbExp=2; IntAct=EBI-1104674, EBI-852851; P37231:PPARG; NbExp=3; IntAct=EBI-1104674, EBI-781384;
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 (By similarity). 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.
TISSUE SPECIFICITY: Detected in blood plasma, cerebrospinal fluid, milk, seminal plasma and colon mucosa. Detected in the germinal center of colon lymphoid nodules and in colon parasympathetic ganglia of the Auerbach plexus (at protein level). Ubiquitous. Detected in brain, testis, ovary, liver and pancreas, and at lower levels in kidney, heart, spleen and lung.
INDUCTION: Up-regulated in response to enterovirus 71 (EV71) infection (at protein level). Up-regulated by agents that induce apoptosis, both at mRNA and protein level. Isoform 1 is up- regulated by androgen. Isoform 2 is down-regulated by androgen.
PTM: Isoform 1 is proteolytically cleaved on its way through the secretory system, probably within the Golgi lumen.
PTM: Polyubiquitinated, leading to proteasomal degradation.
PTM: Heavily N-glycosylated. About 30% of the protein mass is comprised of complex N-linked carbohydrate.
SIMILARITY: Belongs to the clusterin family.
SEQUENCE CAUTION: Sequence=AAA35692.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAB06508.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAB06508.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence; Sequence=AAH10514.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAH19588.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAP88927.1; Type=Erroneous gene model prediction; Sequence=AAP88927.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAT08041.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAG36598.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=CAA32847.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/clu/";

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: CLU
Diseases sorted by gene-association score: follicular dendritic cell sarcoma (17), transient neonatal neutropenia (10), testicular seminoma (10), al amyloidosis (10), pediatric multiple sclerosis (10), ovarian cystadenoma (10), fuchs' endothelial dystrophy (10), lipoprotein glomerulopathy (9), scrapie (9), anaplastic large cell lymphoma (8), congenital disorder of glycosylation, type in (8), pick disease (8), exfoliation syndrome (7), phacogenic glaucoma (6), congenital disorder of glycosylation, type ia (6), tenosynovial giant cell tumor (6), histiocytic and dendritic cell cancer (6), reticulosarcoma (6), homocysteinemia (6), retinal hemangioblastoma (5), ureteral obstruction (5), juxtacortical osteosarcoma (4), peripheral osteosarcoma (4), fructose intolerance, hereditary (4), wallerian degeneration (3), mycosis fungoides (3), alzheimer disease (2), bladder cancer, somatic (2), renal cell carcinoma (2), prostate cancer (2), ovarian cancer, somatic (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 699.29 RPKM in Brain - Caudate (basal ganglia)
Total median expression: 13695.25 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -27.6075-0.368 Picture PostScript Text
3' UTR -360.701324-0.272 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR016016 - Clusterin
IPR000753 - Clusterin-like
IPR016015 - Clusterin_C
IPR016014 - Clusterin_N

Pfam Domains:
PF01093 - Clusterin

ModBase Predicted Comparative 3D Structure on P10909
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001540 beta-amyloid binding
GO:0005515 protein binding
GO:0031625 ubiquitin protein ligase binding
GO:0044877 macromolecular complex binding
GO:0046982 protein heterodimerization activity
GO:0048156 tau protein binding
GO:0050750 low-density lipoprotein particle receptor binding
GO:0051087 chaperone binding
GO:0051787 misfolded protein binding
GO:0016887 ATPase activity

Biological Process:
GO:0000902 cell morphogenesis
GO:0001774 microglial cell activation
GO:0001836 release of cytochrome c from mitochondria
GO:0002376 immune system process
GO:0002576 platelet degranulation
GO:0006629 lipid metabolic process
GO:0006915 apoptotic process
GO:0006956 complement activation
GO:0006958 complement activation, classical pathway
GO:0009615 response to virus
GO:0010628 positive regulation of gene expression
GO:0017038 protein import
GO:0019730 antimicrobial humoral response
GO:0030449 regulation of complement activation
GO:0032286 central nervous system myelin maintenance
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032463 negative regulation of protein homooligomerization
GO:0032464 positive regulation of protein homooligomerization
GO:0032760 positive regulation of tumor necrosis factor production
GO:0043065 positive regulation of apoptotic process
GO:0043691 reverse cholesterol transport
GO:0045087 innate immune response
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0048260 positive regulation of receptor-mediated endocytosis
GO:0050821 protein stabilization
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051131 chaperone-mediated protein complex assembly
GO:0051788 response to misfolded protein
GO:0060548 negative regulation of cell death
GO:0061077 chaperone-mediated protein folding
GO:0061518 microglial cell proliferation
GO:0061740 protein targeting to lysosome involved in chaperone-mediated autophagy
GO:0061741 chaperone-mediated protein transport involved in chaperone-mediated autophagy
GO:0090201 negative regulation of release of cytochrome c from mitochondria
GO:0097193 intrinsic apoptotic signaling pathway
GO:1900221 regulation of beta-amyloid clearance
GO:1901214 regulation of neuron death
GO:1901216 positive regulation of neuron death
GO:1902004 positive regulation of beta-amyloid formation
GO:1902230 negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage
GO:1902430 negative regulation of beta-amyloid formation
GO:1902847 regulation of neuronal signal transduction
GO:1902949 positive regulation of tau-protein kinase activity
GO:1902998 positive regulation of neurofibrillary tangle assembly
GO:1903573 negative regulation of response to endoplasmic reticulum stress
GO:2000060 positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005783 endoplasmic reticulum
GO:0005794 Golgi apparatus
GO:0005829 cytosol
GO:0009986 cell surface
GO:0016020 membrane
GO:0031012 extracellular matrix
GO:0031093 platelet alpha granule lumen
GO:0031410 cytoplasmic vesicle
GO:0031966 mitochondrial membrane
GO:0032991 macromolecular complex
GO:0034366 spherical high-density lipoprotein particle
GO:0042583 chromaffin granule
GO:0043231 intracellular membrane-bounded organelle
GO:0048471 perinuclear region of cytoplasm
GO:0070062 extracellular exosome
GO:0072562 blood microparticle
GO:0097418 neurofibrillary tangle
GO:0097440 apical dendrite
GO:0005856 cytoskeleton
GO:0071944 cell periphery


-  Descriptions from all associated GenBank mRNAs
  LP896518 - Sequence 1382 from Patent EP3253886.
GQ891391 - Homo sapiens clone HEL-S-60 epididymis secretory sperm binding protein mRNA, complete cds.
AY513288 - Homo sapiens aging-associated protein 4 (AAG4) mRNA, complete cds.
AK301324 - Homo sapiens cDNA FLJ57622 complete cds, highly similar to Clusterin precursor.
BC013221 - Homo sapiens clusterin, mRNA (cDNA clone IMAGE:4149765).
BC019588 - Homo sapiens clusterin, mRNA (cDNA clone MGC:24903 IMAGE:4915444), complete cds.
X14723 - Human SP-40,40 mRNA for complement-associated protein SP-40,40 alpha-1 and beta-1 chain.
BX648414 - Homo sapiens mRNA; cDNA DKFZp686L07235 (from clone DKFZp686L07235).
BC010514 - Homo sapiens clusterin, mRNA (cDNA clone MGC:18080 IMAGE:4150452), complete cds.
BC029972 - Homo sapiens clusterin, mRNA (cDNA clone IMAGE:4939961).
AK093399 - Homo sapiens cDNA FLJ36080 fis, clone TESTI2019872, highly similar to CLUSTERIN PRECURSOR.
M74816 - Human sulfated glycoprotein-2 mRNA, 3'end.
J02908 - Human apolipoprotein J mRNA, complete cds.
M64722 - Human TRPM-2 mRNA, complete cds.
JD193272 - Sequence 174296 from Patent EP1572962.
JD383797 - Sequence 364821 from Patent EP1572962.
JD520334 - Sequence 501358 from Patent EP1572962.
JD118895 - Sequence 99919 from Patent EP1572962.
JD155749 - Sequence 136773 from Patent EP1572962.
JD260649 - Sequence 241673 from Patent EP1572962.
M25915 - Human complement cytolysis inhibitor (CLI) mRNA, complete cds.
AK313870 - Homo sapiens cDNA, FLJ94503, highly similar to Homo sapiens clusterin (complement lysis inhibitor, SP-40,40,sulfated glycoprotein 2, testosterone-repressed prostate message 2,apolipoprotein J) (CLU), mRNA.
DQ894623 - Synthetic construct Homo sapiens clone IMAGE:100009083; FLH177010.01L; RZPDo839C01123D clusterin (CLU) gene, encodes complete protein.
KJ890929 - Synthetic construct Homo sapiens clone ccsbBroadEn_00323 CLU gene, encodes complete protein.
KR709373 - Synthetic construct Homo sapiens clone CCSBHm_00001275 CLU (CLU) mRNA, encodes complete protein.
DQ891445 - Synthetic construct clone IMAGE:100004075; FLH177013.01X; RZPDo839C01124D clusterin (CLU) gene, encodes complete protein.
AB527877 - Synthetic construct DNA, clone: pF1KB0447, Homo sapiens CLU gene for clusterin, without stop codon, in Flexi system.
JD021677 - Sequence 2701 from Patent EP1572962.
JD030896 - Sequence 11920 from Patent EP1572962.
CU679733 - Synthetic construct Homo sapiens gateway clone IMAGE:100019453 5' read CLU mRNA.
M26639 - Human sulfated glycoprotein 2 mRNA, partial cds.
JD180052 - Sequence 161076 from Patent EP1572962.
BC039442 - Homo sapiens cDNA clone IMAGE:5304059, with apparent retained intron.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P10909 (Reactome details) participates in the following event(s):

R-HSA-481007 Exocytosis of platelet alpha granule contents
R-HSA-8852580 Clusterin binds C5b-C7, C8, C9
R-HSA-6810643 EPPIN protein complex binds bacteria
R-HSA-114608 Platelet degranulation
R-HSA-977606 Regulation of Complement cascade
R-HSA-76005 Response to elevated platelet cytosolic Ca2+
R-HSA-6803157 Antimicrobial peptides
R-HSA-166658 Complement cascade
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-168249 Innate Immune System
R-HSA-109582 Hemostasis
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: AAG4, APOJ, B2R9Q1, B3KSE6, CLI, CLUS_HUMAN, ENST00000316403.1, ENST00000316403.10, ENST00000316403.11, ENST00000316403.12, ENST00000316403.13, ENST00000316403.14, ENST00000316403.2, ENST00000316403.3, ENST00000316403.4, ENST00000316403.5, ENST00000316403.6, ENST00000316403.7, ENST00000316403.8, ENST00000316403.9, KUB1, NR_045494, P10909, P11380, P11381, Q2TU75, Q5HYC1, Q7Z5B9, uc003xfz.1, uc003xfz.2, uc003xfz.3, uc003xfz.4
UCSC ID: ENST00000316403.15
RefSeq Accession: NM_001831
Protein: P10909 (aka CLUS_HUMAN)
CCDS: CCDS47832.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.