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/";
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.
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.
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
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Common Gene Haplotype Alleles 
