Gene/Proteome Database (LMPD)
LMPD ID
LMP004249
Gene ID
Species
Mus musculus (Mouse)
Gene Name
clusterin
Gene Symbol
Synonyms
AI893575; ApoJ; Cli; D14Ucla3; SP-40; Sgp-2; Sgp2; Sugp-2
Alternate Names
clusterin; apo-J; clustrin; Apolipoprotein J; sulfated glycoprotein 2; complement lysis inhibitor; testosterone repressed prostate message; testosterone repressed prostate message-2
Chromosome
14
Map Location
14 D1|14 34.36 cM
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. [provided by RefSeq, May 2011]
Orthologs
Proteins
clusterin precursor | |
---|---|
Refseq ID | NP_038520 |
Protein GI | 214010170 |
UniProt ID | Q06890 |
mRNA ID | NM_013492 |
Length | 448 |
RefSeq Status | VALIDATED |
MKILLLCVALLLIWDNGMVLGEQEVSDNELQELSTQGSRYINKEIQNAVQGVKHIKTLIEKTNAERKSLLNSLEEAKKKKEDALEDTRDSEMKLKAFPEVCNETMMALWEECKPCLKHTCMKFYARVCRSGSGLVGQQLEEFLNQSSPFYFWMNGDRIDSLLESDRQQSQVLDAMQDSFARASGIIDTLFQDRFFARELHDPHYFSPIGFPHKRPHFLYPKSRLVRSLMSPSHYGPPSFHNMFQPFFEMIHQAQQAMDVQLHSPAFQFPDVDFLREGEDDRTVCKEIRRNSTGCLKMKGQCEKCQEILSVDCSTNNPAQANLRQELNDSLQVAERLTEQYKELLQSFQSKMLNTSSLLEQLNDQFNWVSQLANLTQGEDKYYLRVSTVTTHSSDSEVPSRVTEVVVKLFDSDPITVVLPEEVSKDNPKFMDTVAEKALQEYRRKSRAE | |
sig_peptide: 1..21 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2329 peptide sequence: MKILLLCVALLLIWDNGMVLG mat_peptide: 22..448 product: Clusterin experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (Q06890.1) calculated_mol_wt: 49345 peptide sequence: EQEVSDNELQELSTQGSRYINKEIQNAVQGVKHIKTLIEKTNAERKSLLNSLEEAKKKKEDALEDTRDSEMKLKAFPEVCNETMMALWEECKPCLKHTCMKFYARVCRSGSGLVGQQLEEFLNQSSPFYFWMNGDRIDSLLESDRQQSQVLDAMQDSFARASGIIDTLFQDRFFARELHDPHYFSPIGFPHKRPHFLYPKSRLVRSLMSPSHYGPPSFHNMFQPFFEMIHQAQQAMDVQLHSPAFQFPDVDFLREGEDDRTVCKEIRRNSTGCLKMKGQCEKCQEILSVDCSTNNPAQANLRQELNDSLQVAERLTEQYKELLQSFQSKMLNTSSLLEQLNDQFNWVSQLANLTQGEDKYYLRVSTVTTHSSDSEVPSRVTEVVVKLFDSDPITVVLPEEVSKDNPKFMDTVAEKALQEYRRKSRAE |
Gene Information
Gene Ontology (GO Annotations)
GO ID | Source | Type | Description |
---|---|---|---|
GO:0097440 | ISS:Alzheimers_University_of_Toronto | C | apical dendrite |
GO:0072562 | IEA:Ensembl | C | blood microparticle |
GO:0005737 | ISS:Alzheimers_University_of_Toronto | C | cytoplasm |
GO:0031410 | IEA:UniProtKB-KW | C | cytoplasmic vesicle |
GO:0005783 | IEA:UniProtKB-KW | C | endoplasmic reticulum |
GO:0031012 | IEA:Ensembl | C | extracellular matrix |
GO:0005615 | ISS:UniProtKB | C | extracellular space |
GO:0070062 | IEA:Ensembl | C | extracellular vesicular exosome |
GO:0016020 | IEA:UniProtKB-KW | C | membrane |
GO:0005739 | IEA:UniProtKB-KW | C | mitochondrion |
GO:0097418 | ISS:Alzheimers_University_of_Toronto | C | neurofibrillary tangle |
GO:0005634 | IEA:UniProtKB-KW | C | nucleus |
GO:0048471 | ISS:UniProtKB | C | perinuclear region of cytoplasm |
GO:0034366 | ISS:UniProtKB | C | spherical high-density lipoprotein particle |
GO:0051787 | ISS:UniProtKB | F | misfolded protein binding |
GO:0031625 | ISS:UniProtKB | F | ubiquitin protein ligase binding |
GO:0000902 | ISS:Alzheimers_University_of_Toronto | P | cell morphogenesis |
GO:0032286 | ISS:Alzheimers_University_of_Toronto | P | central nervous system myelin maintenance |
GO:0051131 | ISS:Alzheimers_University_of_Toronto | P | chaperone-mediated protein complex assembly |
GO:0061077 | ISS:UniProtKB | P | chaperone-mediated protein folding |
GO:0097193 | ISS:UniProtKB | P | intrinsic apoptotic signaling pathway |
GO:0001774 | ISS:Alzheimers_University_of_Toronto | P | microglial cell activation |
GO:0061518 | ISS:Alzheimers_University_of_Toronto | P | microglial cell proliferation |
GO:1902430 | ISS:Alzheimers_University_of_Toronto | P | negative regulation of beta-amyloid formation |
GO:1902230 | ISS:BHF-UCL | P | negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage |
GO:0032463 | ISS:UniProtKB | P | negative regulation of protein homooligomerization |
GO:0051092 | ISS:UniProtKB | P | positive regulation of NF-kappaB transcription factor activity |
GO:0043065 | ISS:UniProtKB | P | positive regulation of apoptotic process |
GO:1902004 | IMP:Alzheimers_University_of_Toronto | P | positive regulation of beta-amyloid formation |
GO:2001244 | ISS:UniProtKB | P | positive regulation of intrinsic apoptotic signaling pathway |
GO:1902998 | ISS:Alzheimers_University_of_Toronto | P | positive regulation of neurofibrillary tangle assembly |
GO:1901216 | IMP:Alzheimers_University_of_Toronto | P | positive regulation of neuron death |
GO:0045429 | ISS:Alzheimers_University_of_Toronto | P | positive regulation of nitric oxide biosynthetic process |
GO:0032436 | ISS:UniProtKB | P | positive regulation of proteasomal ubiquitin-dependent protein catabolic process |
GO:2000060 | ISS:UniProtKB | P | positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process |
GO:1902949 | ISS:Alzheimers_University_of_Toronto | P | positive regulation of tau-protein kinase activity |
GO:0032760 | ISS:Alzheimers_University_of_Toronto | P | positive regulation of tumor necrosis factor production |
GO:0017038 | ISS:Alzheimers_University_of_Toronto | P | protein import |
GO:0050821 | ISS:UniProtKB | P | protein stabilization |
GO:1900221 | ISS:Alzheimers_University_of_Toronto | P | regulation of beta-amyloid clearance |
GO:1901214 | ISS:Alzheimers_University_of_Toronto | P | regulation of neuron death |
GO:1902847 | ISS:Alzheimers_University_of_Toronto | P | regulation of neuronal signal transduction |
GO:0051788 | ISS:UniProtKB | P | response to misfolded protein |
GO:0009615 | IEA:Ensembl | P | response to virus |
REACTOME Pathway Links
Domain Information
UniProt Annotations
Entry Information
Comments
Comment Type | Description |
---|---|
Disruption Phenotype | No visible phenotype. During myocarditis, mice show an increased tendency to cardiac tissue injury. {ECO:0000269|PubMed:11067863}. |
Function | 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. When secreted, protects cells against apoptosis and against cytolysis by complement. Intracellular forms 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. Promotes apoptosis when in the nucleus. Inhibits apoptosis when associated with the mitochondrial membrane by interference with BAX-dependent release of cytochrome c into the cytoplasm. Plays a role in the regulation of cell proliferation (By similarity). {ECO:0000250}. |
Ptm | Extensively glycosylated with sulfated N-linked carbohydrates. {ECO:0000269|PubMed:16944957, ECO:0000269|PubMed:17330941}. |
Ptm | Polyubiquitinated, leading to proteasomal degradation. {ECO:0000250}. |
Ptm | Proteolytically cleaved on its way through the secretory system, probably within the Golgi lumen. {ECO:0000250}. |
Similarity | Belongs to the clusterin family. {ECO:0000305}. |
Subcellular Location | Secreted {ECO:0000269|PubMed:12551933}. Nucleus {ECO:0000269|PubMed:12551933}. Cytoplasm {ECO:0000269|PubMed:12551933}. Mitochondrion membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Cytoplasm, cytosol {ECO:0000269|PubMed:12551933}. Microsome {ECO:0000250}. Endoplasmic reticulum {ECO:0000250}. Cytoplasmic vesicle, secretory vesicle, chromaffin granule {ECO:0000250}. Note=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 (By similarity). {ECO:0000250}. |
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 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 (By similarity). Interacts (via alpha chain) with XRCC6. Found in a complex with LTF, CLU, EPPIN and SEMG1 (By similarity). {ECO:0000250}. |
Tissue Specificity | Most abundant in stomach, liver, brain, and testis, with intermediate levels in heart, ovary and kidney. |
Identical and Related Proteins
Unique RefSeq proteins for LMP004249 (as displayed in Record Overview)
Protein GI | Database | Accession | Length | Protein Name |
---|---|---|---|---|
214010170 | RefSeq | NP_038520 | 448 | clusterin precursor |
Identical Sequences to LMP004249 proteins
Reference | Database | Accession | Length | Protein Name |
---|---|---|---|---|
GI:214010170 | DBBJ | BAA03162.1 | 448 | sulfated glycoprotein-2 [Mus musculus] |
GI:214010170 | GenBank | AAF06365.1 | 448 | clusterin [Mus musculus] |
GI:214010170 | GenBank | AAF67184.1 | 448 | sulfated glycoprotein-2 isoform 1 [Mus musculus] |
GI:214010170 | GenBank | AAH75668.1 | 448 | Clusterin [Mus musculus] |
GI:214010170 | RefSeq | XP_006518567.1 | 448 | PREDICTED: clusterin isoform X2 [Mus musculus] |
GI:214010170 | SwissProt | Q06890.1 | 448 | RecName: Full=Clusterin; AltName: Full=Apolipoprotein J; Short=Apo-J; AltName: Full=Clustrin; AltName: Full=Sulfated glycoprotein 2; Short=SGP-2; Contains: RecName: Full=Clusterin beta chain; Contains: RecName: Full=Clusterin alpha chain; Flags: Precursor [Mus musculus] |
Related Sequences to LMP004249 proteins
Reference | Database | Accession | Length | Protein Name |
---|---|---|---|---|
GI:214010170 | GenBank | AAA37284.1 | 448 | clustrin [Mus musculus] |
GI:214010170 | GenBank | AAB30623.1 | 448 | apolipoprotein J [Mus sp.] |
GI:214010170 | GenBank | EDL01130.1 | 419 | clusterin, partial [Mus musculus] |
GI:214010170 | GenBank | EDL85369.1 | 447 | clusterin, isoform CRA_a [Rattus norvegicus] |
GI:214010170 | GenBank | EDL85371.1 | 447 | clusterin, isoform CRA_a [Rattus norvegicus] |
GI:214010170 | RefSeq | XP_006518566.1 | 458 | PREDICTED: clusterin isoform X1 [Mus musculus] |