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MGP000588

UniProt Annotations

Entry Information
Gene Nameclusterin
Protein EntryCLUS_HUMAN
UniProt IDP10909
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=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;
FunctionIsoform 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:0000269|PubMed:11123922, ECO:0000269|PubMed:12047389, ECO:0000269|PubMed:12176985, ECO:0000269|PubMed:12551933, ECO:0000269|PubMed:12882985, ECO:0000269|PubMed:16113678, ECO:0000269|PubMed:17260971, ECO:0000269|PubMed:17407782, ECO:0000269|PubMed:17412999, ECO:0000269|PubMed:17689225, ECO:0000269|PubMed:19137541, ECO:0000269|PubMed:19535339, ECO:0000269|PubMed:19996109, ECO:0000269|PubMed:20068069, ECO:0000269|PubMed:21505792}.
InductionUp-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:0000269|PubMed:16548883, ECO:0000269|PubMed:17148459, ECO:0000269|PubMed:17689225}.
InteractionQ07817-1: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;
PtmHeavily N-glycosylated. About 30% of the protein mass is comprised of complex N-linked carbohydrate. {ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:1551440, ECO:0000269|PubMed:16263699, ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:16740002, ECO:0000269|PubMed:17260971, ECO:0000269|PubMed:18780401, ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:2387851, ECO:0000269|PubMed:9336835}.
PtmIsoform 1 is proteolytically cleaved on its way through the secretory system, probably within the Golgi lumen. {ECO:0000269|PubMed:2387851}.
PtmPolyubiquitinated, leading to proteasomal degradation. {ECO:0000269|PubMed:17451556, ECO:0000269|PubMed:19137541}.
Sequence CautionSequence=AAA35692.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAB06508.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAB06508.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence.; Evidence={ECO:0000305}; Sequence=AAH10514.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAH19588.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAP88927.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAP88927.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAT08041.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAG36598.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=CAA32847.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
SimilarityBelongs to the clusterin family. {ECO:0000305}.
Subcellular LocationIsoform 1: Secreted. Note=Can retrotranslocate from the secretory compartments to the cytosol upon cellular stress.
Subcellular LocationNucleus. Cytoplasm. Mitochondrion membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm, cytosol. Microsome. Endoplasmic reticulum. Cytoplasmic vesicle, secretory vesicle, chromaffin granule {ECO:0000250}. 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.
SubunitAntiparallel 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:0000269|PubMed:12047389, ECO:0000269|PubMed:12176985, ECO:0000269|PubMed:12551933, ECO:0000269|PubMed:1491011, ECO:0000269|PubMed:15480429, ECO:0000269|PubMed:1551440, ECO:0000269|PubMed:16113678, ECO:0000269|PubMed:17260971, ECO:0000269|PubMed:17407782, ECO:0000269|PubMed:17412999, ECO:0000269|PubMed:1742316, ECO:0000269|PubMed:17451556, ECO:0000269|PubMed:17567961, ECO:0000269|PubMed:1903064, ECO:0000269|PubMed:19535339, ECO:0000269|PubMed:1974459, ECO:0000269|PubMed:20068069, ECO:0000269|PubMed:2387851, ECO:0000269|PubMed:2780565, ECO:0000269|PubMed:8292612, ECO:0000269|PubMed:8328966}.
Tissue SpecificityDetected 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:0000269|PubMed:11123922, ECO:0000269|PubMed:17260971, ECO:0000269|PubMed:17322305, ECO:0000269|PubMed:17412999, ECO:0000269|PubMed:1974459, ECO:0000269|PubMed:2387851, ECO:0000269|PubMed:2780565, ECO:0000269|PubMed:3154963, ECO:0000269|PubMed:8181474, ECO:0000269|PubMed:8292612, ECO:0000269|PubMed:8328966}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CLUID40107ch8p21.html";
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/clu/";
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