Clusterin (Protein name
), CLUS_HUMAN from NCBI database.
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Gene name:
CLU(AAG4;APOJ;CLI;KUB1);
Protein name:
Clusterin;
Alternative:
Apolipoprotein J(Apo-J);Aging-associated gene 4 protein;Complement-associated protein SP-40,40;Complement cytolysis inhibitor(CLI);NA1/NA2;Ku70-binding protein 1;Testosterone-repressed prostate message 2(TRPM-2);
Organism:
Human (Homo sapiens).
General Annotation
Sub Unit:
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.
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.
Subcellular Location:
Nucleus
Cytoplasm
Mitochondrion membrane
Peripheral membrane protein
Cytoplasmic side
Cytoplasm
cytosol
Microsome
Endoplasmic reticulum
Cytoplasmic vesicle
secretory vesicle
chromaffin granule
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.
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Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1);PROTEIN SEQUENCE OF N-TERMINUS;SUBUNIT;DISULFIDE BONDS;SUBCELLULAR LOCATION;TISSUE SPECIFICITY
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Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA];PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2);TISSUE SPECIFICITY
"Full-length cDNA libraries and normalization." Li W.B.
,
Gruber C.
,
Jessee J.
,
Polayes D.
Submitted (2004-07) to the EMBL/GenBank/DDBJ databases
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)
NIEHS SNPs program
Submitted (2003-07) to the EMBL/GenBank/DDBJ databases
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Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA];VARIANTS HIS-317; ASN-328 AND LEU-396
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Cited for: PROTEIN SEQUENCE OF 23-33; 229-242; 303-317 AND 397-403;SUBUNIT;INTERACTION WITH APOA1
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Cited for: PROTEIN SEQUENCE OF 23-52 AND 228-257;SUBUNIT;DISULFIDE BOND;PROTEOLYTIC PROCESSING;GLYCOSYLATION;SUBCELLULAR LOCATION;TISSUE SPECIFICITY
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Cited for: PROTEIN SEQUENCE OF 23-41 AND 228-246;INTERACTION WITH APP;SUBCELLULAR LOCATION;DISULFIDE BOND;TISSUE SPECIFICITY
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Cited for: PROTEIN SEQUENCE OF 23-33 AND 228-240;SUBCELLULAR LOCATION;TISSUE SPECIFICITY
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Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 34-449 (ISOFORMS 1/2/4);PARTIAL PROTEIN SEQUENCE;SUBUNIT;TISSUE SPECIFICITY
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Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2);PARTIAL PROTEIN SEQUENCE
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Cited for: PARTIAL PROTEIN SEQUENCE;DISULFIDE BONDS;GLYCOSYLATION AT ASN-86; ASN-103; ASN-145; ASN-291; ASN-354 AND ASN-374
19.
"Identification of human aging-associated gene." Kim J.W.
Submitted (2003-12) to the EMBL/GenBank/DDBJ databases
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Cited for: PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)
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Cited for: INTERACTION WITH PON1;SUBCELLULAR LOCATION;TISSUE SPECIFICITY
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Cited for: GLYCOSYLATION AT ASN-86; ASN-103; ASN-145; ASN-291; ASN-354 AND ASN-374
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Cited for: FUNCTION;SUBCELLULAR LOCATION;ABSENCE OF ATPASE ACTIVITY;TISSUE SPECIFICITY
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Cited for: ALTERNATIVE SPLICING;IDENTIFICATION OF ISOFORM 4;FUNCTION;INTERACTION WITH XRCC6;SUBCELLULAR LOCATION
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Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-354 AND ASN-374
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Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-86; ASN-103; ASN-145; ASN-291; ASN-354 AND ASN-374
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Cited for: FUNCTION;SUBCELLULAR LOCATION;INTERACTION WITH BAX
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Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-374
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Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-374
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Cited for: FUNCTION;SUBUNIT;INTERACTION WITH LRP2;GLYCOSYLATION;SUBCELLULAR LOCATION;IDENTIFICATION BY MASS SPECTROMETRY;CIRCULAR DICHROISM;TISSUE SPECIFICITY
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Cited for: FUNCTION;INDUCTION;PROTEASOMAL DEGRADATION;SUBCELLULAR LOCATION
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Cited for: IDENTIFICATION IN A COMPLEX WITH LTF; SEMG1 AND EPPIN
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Cited for: FUNCTION;SUBUNIT;SUBCELLULAR LOCATION;TISSUE SPECIFICITY
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Cited for: ALTERNATIVE SPLICING;IDENTIFICATION OF ISOFORMS 1 AND 2;INDUCTION BY ANDROGEN
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Cited for: ALTERNATIVE SPLICING;IDENTIFICATION OF ISOFORMS 1; 2 AND 5;TISSUE SPECIFICITY
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Cited for: SUBCELLULAR LOCATION;INTERACTION WITH SYVN1;UBIQUITINATION
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Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-291; ASN-317 AND ASN-374
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Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-86; ASN-103; ASN-145; ASN-354 AND ASN-374
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Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-374;STRUCTURE OF CARBOHYDRATES
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Cited for: FUNCTION;SUBCELLULAR LOCATION;INTERACTION WITH COMMD1; UBIQUITIN; CUL1 ANDBTRC;IDENTIFICATION IN A E3 UBIQUITIN-PROTEIN LIGASE COMPLEX