Gene/Proteome Database (LMPD)

LMPD ID
LMP002570
Gene ID
1191
Species
Homo sapiens (Human)
Gene Name
clusterin
Gene Symbol
CLU
Synonyms
APO-J; APOJ; CLI; CLU1; CLU2; KUB1; NA1/NA2; SGP-2; SGP2; SP-40; TRPM-2; TRPM2
Alternate Names
clusterin; apolipoprotein J; ku70-binding protein 1; sulfated glycoprotein 2; aging-associated protein 4; complement lysis inhibitor; complement cytolysis inhibitor; complement-associated protein SP-40,40; testosterone-repressed prostate message 2
Chromosome
8
Map Location
8p21-p12
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]
Orthologs
View orthologs and multiple alignments for CLU

Proteins

clusterin preproprotein
Refseq ID NP_001822
Protein GI 355594753
UniProt ID P10909
mRNA ID NM_001831
Length 449
RefSeq Status REVIEWED
MMKTLLLFVGLLLTWESGQVLGDQTVSDNELQEMSNQGSKYVNKEIQNAVNGVKQIKTLIEKTNEERKTLLSNLEEAKKKKEDALNETRESETKLKELPGVCNETMMALWEECKPCLKQTCMKFYARVCRSGSGLVGRQLEEFLNQSSPFYFWMNGDRIDSLLENDRQQTHMLDVMQDHFSRASSIIDELFQDRFFTREPQDTYHYLPFSLPHRRPHFFFPKSRIVRSLMPFSPYEPLNFHAMFQPFLEMIHEAQQAMDIHFHSPAFQHPPTEFIREGDDDRTVCREIRHNSTGCLRMKDQCDKCREILSVDCSTNNPSQAKLRRELDESLQVAERLTRKYNELLKSYQWKMLNTSSLLEQLNEQFNWVSRLANLTQGEDQYYLRVTTVASHTSDSDVPSGVTEVVVKLFDSDPITVTVPVEVSRKNPKFMETVAEKALQEYRKKHREE
sig_peptide: 1..22 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2450 peptide sequence: MMKTLLLFVGLLLTWESGQVLG mat_peptide: 23..449 product: Clusterin experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (P10909.1) calculated_mol_wt: 50063 peptide sequence: DQTVSDNELQEMSNQGSKYVNKEIQNAVNGVKQIKTLIEKTNEERKTLLSNLEEAKKKKEDALNETRESETKLKELPGVCNETMMALWEECKPCLKQTCMKFYARVCRSGSGLVGRQLEEFLNQSSPFYFWMNGDRIDSLLENDRQQTHMLDVMQDHFSRASSIIDELFQDRFFTREPQDTYHYLPFSLPHRRPHFFFPKSRIVRSLMPFSPYEPLNFHAMFQPFLEMIHEAQQAMDIHFHSPAFQHPPTEFIREGDDDRTVCREIRHNSTGCLRMKDQCDKCREILSVDCSTNNPSQAKLRRELDESLQVAERLTRKYNELLKSYQWKMLNTSSLLEQLNEQFNWVSRLANLTQGEDQYYLRVTTVASHTSDSDVPSGVTEVVVKLFDSDPITVTVPVEVSRKNPKFMETVAEKALQEYRKKHREE mat_peptide: 23..227 product: Clusterin beta chain experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (P10909.1) calculated_mol_wt: 24198 peptide sequence: DQTVSDNELQEMSNQGSKYVNKEIQNAVNGVKQIKTLIEKTNEERKTLLSNLEEAKKKKEDALNETRESETKLKELPGVCNETMMALWEECKPCLKQTCMKFYARVCRSGSGLVGRQLEEFLNQSSPFYFWMNGDRIDSLLENDRQQTHMLDVMQDHFSRASSIIDELFQDRFFTREPQDTYHYLPFSLPHRRPHFFFPKSRIVR mat_peptide: 228..449 product: Clusterin alpha chain experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (P10909.1) calculated_mol_wt: 25883 peptide sequence: SLMPFSPYEPLNFHAMFQPFLEMIHEAQQAMDIHFHSPAFQHPPTEFIREGDDDRTVCREIRHNSTGCLRMKDQCDKCREILSVDCSTNNPSQAKLRRELDESLQVAERLTRKYNELLKSYQWKMLNTSSLLEQLNEQFNWVSRLANLTQGEDQYYLRVTTVASHTSDSDVPSGVTEVVVKLFDSDPITVTVPVEVSRKNPKFMETVAEKALQEYRKKHREE

Gene Information

Entrez Gene ID
1191
Gene Name
clusterin
Gene Symbol
CLU
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0097440 IDA:Alzheimers_University_of_Toronto C apical dendrite
GO:0072562 IDA:UniProt C blood microparticle
GO:0005737 IDA:Alzheimers_University_of_Toronto C cytoplasm
GO:0005783 IEA:UniProtKB-KW C endoplasmic reticulum
GO:0031012 IDA:UniProtKB C extracellular matrix
GO:0005576 TAS:Reactome C extracellular region
GO:0005615 IDA:UniProtKB C extracellular space
GO:0070062 IDA:UniProtKB C extracellular vesicular exosome
GO:0016020 IEA:UniProtKB-KW C membrane
GO:0005739 IDA:BHF-UCL C mitochondrion
GO:0097418 IDA:Alzheimers_University_of_Toronto C neurofibrillary tangle
GO:0005634 IEA:UniProtKB-KW C nucleus
GO:0048471 IDA:UniProtKB C perinuclear region of cytoplasm
GO:0031093 TAS:Reactome C platelet alpha granule lumen
GO:0034366 IDA:BHF-UCL C spherical high-density lipoprotein particle
GO:0051787 IDA:UniProtKB F misfolded protein binding
GO:0031625 IDA:UniProtKB F ubiquitin protein ligase binding
GO:0007596 TAS:Reactome P blood coagulation
GO:0000902 IDA:Alzheimers_University_of_Toronto P cell morphogenesis
GO:0032286 IMP:Alzheimers_University_of_Toronto P central nervous system myelin maintenance
GO:0051131 IDA:Alzheimers_University_of_Toronto P chaperone-mediated protein complex assembly
GO:0061077 IDA:UniProtKB P chaperone-mediated protein folding
GO:0006956 TAS:ProtInc P complement activation
GO:0006958 IEA:UniProtKB-KW P complement activation, classical pathway
GO:0045087 IEA:UniProtKB-KW P innate immune response
GO:0097193 IDA:UniProtKB P intrinsic apoptotic signaling pathway
GO:0006629 NAS:ProtInc P lipid metabolic process
GO:0001774 IDA:Alzheimers_University_of_Toronto P microglial cell activation
GO:0061518 IDA:Alzheimers_University_of_Toronto P microglial cell proliferation
GO:1902430 IDA:Alzheimers_University_of_Toronto P negative regulation of beta-amyloid formation
GO:1902230 IMP:BHF-UCL P negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage
GO:0032463 IMP:BHF-UCL P negative regulation of protein homooligomerization
GO:0030168 TAS:Reactome P platelet activation
GO:0002576 TAS:Reactome P platelet degranulation
GO:0051092 IMP:UniProtKB P positive regulation of NF-kappaB transcription factor activity
GO:0043065 IMP:UniProtKB P positive regulation of apoptotic process
GO:1902004 ISS:Alzheimers_University_of_Toronto P positive regulation of beta-amyloid formation
GO:2001244 IMP:UniProtKB P positive regulation of intrinsic apoptotic signaling pathway
GO:1902998 IMP:Alzheimers_University_of_Toronto P positive regulation of neurofibrillary tangle assembly
GO:1901216 IDA:Alzheimers_University_of_Toronto P positive regulation of neuron death
GO:0045429 IDA:Alzheimers_University_of_Toronto P positive regulation of nitric oxide biosynthetic process
GO:0032436 IMP:UniProtKB P positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:2000060 IMP:UniProtKB P positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:1902949 IMP:Alzheimers_University_of_Toronto P positive regulation of tau-protein kinase activity
GO:0032760 IDA:Alzheimers_University_of_Toronto P positive regulation of tumor necrosis factor production
GO:0017038 IDA:Alzheimers_University_of_Toronto P protein import
GO:0050821 IDA:UniProtKB P protein stabilization
GO:1900221 IDA:Alzheimers_University_of_Toronto P regulation of beta-amyloid clearance
GO:1901214 IDA:Alzheimers_University_of_Toronto P regulation of neuron death
GO:1902847 IMP:Alzheimers_University_of_Toronto P regulation of neuronal signal transduction
GO:0001836 IC:BHF-UCL P release of cytochrome c from mitochondria
GO:0051788 IDA:BHF-UCL P response to misfolded protein
GO:0009615 IEP:UniProtKB P response to virus
GO:0043691 TAS:BHF-UCL P reverse cholesterol transport

REACTOME Pathway Links

REACTOME Pathway ID Description
REACT_798 Platelet activation, signaling and aggregation
REACT_318 Platelet degranulation
REACT_1280 Response to elevated platelet cytosolic Ca2+

Domain Information

InterPro Annotations

Accession Description
IPR016016 Clusterin
IPR016015 Clusterin, C-terminal
IPR016014 Clusterin, N-terminal
IPR000753 Clusterin-like

UniProt Annotations

Entry Information

Gene Name
clusterin
Protein Entry
CLUS_HUMAN
UniProt ID
P10909
Species
Human

Comments

Comment Type Description
Alternative Products Event=Alternative splicing; Named isoforms=5; Name=1; Synonyms=2, CLU35, sCLU; IsoId=P10909-1; Sequence=Displayed; Note=Major isoform.; Name=2; Synonyms=1, CLU34; IsoId=P10909-2; Sequence=VSP_037661; Name=3; IsoId=P10909-3; Sequence=VSP_041475; Name=4; Synonyms=nCLU; IsoId=P10909-4; Sequence=VSP_041476; Note=Minor isoform that has been detected in a breast cancer cell line, but not in any other tissues or cell lines.; Name=5; Synonyms=CLU36; IsoId=P10909-5; Sequence=VSP_041477;
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. {ECO
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. {ECO
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;
Ptm Heavily N-glycosylated. About 30% of the protein mass is comprised of complex N-linked carbohydrate. {ECO
Ptm Isoform 1 is proteolytically cleaved on its way through the secretory system, probably within the Golgi lumen.
Ptm Polyubiquitinated, leading to proteasomal degradation.
Sequence Caution Sequence=AAA35692.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ; Sequence=AAB06508.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ; Sequence=AAB06508.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence.; Evidence= ; Sequence=AAH10514.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ; Sequence=AAH19588.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ; Sequence=AAP88927.1; Type=Erroneous gene model prediction; Evidence= ; Sequence=AAP88927.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ; Sequence=AAT08041.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ; Sequence=BAG36598.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ; Sequence=CAA32847.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ;
Similarity Belongs to the clusterin family.
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.
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. {ECO
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. {ECO
Web Resource Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CLUID40107ch8p21.html";
Web Resource Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/clu/";

Identical and Related Proteins

Unique RefSeq proteins for LMP002570 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
355594753 RefSeq NP_001822 449 clusterin preproprotein

Identical Sequences to LMP002570 proteins

Reference Database Accession Length Protein Name
GI:355594753 GenBank AGA52039.1 449 Sequence 11 from patent US 8329399
GI:355594753 GenBank AGM56998.1 449 Sequence 14 from patent US 8420337
GI:355594753 GenBank AGV81884.1 449 Sequence 206 from patent US 8524238
GI:355594753 GenBank AHD78165.1 449 Sequence 25502 from patent US 8586006
GI:355594753 GenBank AHE20650.1 449 Sequence 14 from patent US 8575107
GI:355594753 GenBank AIC48520.1 449 CLU, partial [synthetic construct]

Related Sequences to LMP002570 proteins

Reference Database Accession Length Protein Name
GI:355594753 DBBJ BAI46041.1 501 clusterin, partial [synthetic construct]
GI:355594753 GenBank AFL25856.1 501 Sequence 205 from patent US 8168586
GI:355594753 GenBank AGA52038.1 501 Sequence 10 from patent US 8329399
GI:355594753 GenBank AGV81883.1 501 Sequence 205 from patent US 8524238
GI:355594753 GenBank AHD78164.1 501 Sequence 25501 from patent US 8586006
GI:355594753 RefSeq XP_006716347.1 501 PREDICTED: clusterin isoform X1 [Homo sapiens]