CLUS_MOUSE
ID CLUS_MOUSE Reviewed; 448 AA.
AC Q06890;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Clusterin {ECO:0000303|PubMed:8354695};
DE AltName: Full=Apolipoprotein J {ECO:0000303|PubMed:8169523};
DE Short=Apo-J;
DE AltName: Full=Clustrin {ECO:0000303|Ref.4};
DE AltName: Full=Sulfated glycoprotein 2 {ECO:0000303|PubMed:21183079};
DE Short=SGP-2 {ECO:0000303|PubMed:21183079};
DE Contains:
DE RecName: Full=Clusterin beta chain;
DE Contains:
DE RecName: Full=Clusterin alpha chain;
DE Flags: Precursor;
GN Name=Clu {ECO:0000312|MGI:MGI:88423};
GN Synonyms=Apoj {ECO:0000303|PubMed:8169523}, Msgp-2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=8352774; DOI=10.1006/bbrc.1993.1946;
RA Lee K.-H., Ji Y.-M., Lim H.M., Lee S.-C., You K.-H.;
RT "Molecular cloning and sequencing of sulfated glycoprotein-2 cDNA from
RT testis of mouse: implications of two different mRNAs of SGP-2.";
RL Biochem. Biophys. Res. Commun. 194:1175-1180(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Heart;
RX PubMed=8354695; DOI=10.1083/jcb.122.5.1119;
RA French L.E., Chonn A., Ducrest D., Baumann B., Belin D., Wohlwend A.,
RA Kiss J.Z., Sappino A.P., Tschopp J., Schifferli J.A.;
RT "Murine clusterin: molecular cloning and mRNA localization of a gene
RT associated with epithelial differentiation processes during
RT embryogenesis.";
RL J. Cell Biol. 122:1119-1130(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6 X CBA; TISSUE=Liver;
RX PubMed=8169523;
RA Jordan-Starck T.C., Lund S.D., Witte D.P., Aronow B.J., Ley C.A.,
RA Stuart W.D., Swertfeger D.K., Clayton L.R., Sells S.F., Paigen B.;
RT "Mouse apolipoprotein J: characterization of a gene implicated in
RT atherosclerosis.";
RL J. Lipid Res. 35:194-210(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hodgdon B.A., Min B.H., Yan H., Farris J.A., Foster D.N., Strauch A.R.;
RT "Secretion of sulfated glycoprotein (clustrin) accompanies
RT cytodifferentiation and structural remodeling of mouse BC3H1 myogenic
RT cells.";
RL Submitted (NOV-1992) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=11067863; DOI=10.1172/jci9037;
RA McLaughlin L., Zhu G., Mistry M., Ley-Ebert C., Stuart W.D., Florio C.J.,
RA Groen P.A., Witt S.A., Kimball T.R., Witte D.P., Harmony J.A., Aronow B.J.;
RT "Apolipoprotein J/clusterin limits the severity of murine autoimmune
RT myocarditis.";
RL J. Clin. Invest. 106:1105-1113(2000).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=11865066; DOI=10.1128/mcb.22.6.1893-1902.2002;
RA Rosenberg M.E., Girton R., Finkel D., Chmielewski D., Barrie A. III,
RA Witte D.P., Zhu G., Bissler J.J., Harmony J.A., Aronow B.J.;
RT "Apolipoprotein J/clusterin prevents a progressive glomerulopathy of
RT aging.";
RL Mol. Cell. Biol. 22:1893-1902(2002).
RN [8]
RP INTERACTION WITH XRCC6, SUBCELLULAR LOCATION, MUTAGENESIS OF 78-LYS-LYS-79;
RP LEU-343; 357-LEU-LEU-358; LEU-361; LEU-371 AND 442-ARG-ARG-443, FUNCTION,
RP AND MOTIF.
RX PubMed=12551933; DOI=10.1074/jbc.m209233200;
RA Leskov K.S., Klokov D.Y., Li J., Kinsella T.J., Boothman D.A.;
RT "Synthesis and functional analyses of nuclear clusterin, a cell death
RT protein.";
RL J. Biol. Chem. 278:11590-11600(2003).
RN [9]
RP FUNCTION.
RX PubMed=14741101; DOI=10.1016/s0896-6273(03)00850-x;
RA DeMattos R.B., Cirrito J.R., Parsadanian M., May P.C., O'Dell M.A.,
RA Taylor J.W., Harmony J.A., Aronow B.J., Bales K.R., Paul S.M.,
RA Holtzman D.M.;
RT "ApoE and clusterin cooperatively suppress Abeta levels and deposition:
RT evidence that ApoE regulates extracellular Abeta metabolism in vivo.";
RL Neuron 41:193-202(2004).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-327.
RC STRAIN=C57BL/6J; TISSUE=Plasma;
RX PubMed=16944957; DOI=10.1021/pr060186m;
RA Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.;
RT "Proteome-wide characterization of N-glycosylation events by diagonal
RT chromatography.";
RL J. Proteome Res. 5:2438-2447(2006).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-290.
RC STRAIN=C57BL/6J; TISSUE=Plasma;
RX PubMed=17330941; DOI=10.1021/pr0604559;
RA Bernhard O.K., Kapp E.A., Simpson R.J.;
RT "Enhanced analysis of the mouse plasma proteome using cysteine-containing
RT tryptic glycopeptides.";
RL J. Proteome Res. 6:987-995(2007).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Functions as extracellular chaperone that prevents
CC aggregation of non native proteins. Prevents stress-induced aggregation
CC of blood plasma proteins (By similarity). Inhibits formation of amyloid
CC fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ
CC variants (in vitro) (PubMed:14741101). Does not require ATP. Maintains
CC partially unfolded proteins in a state appropriate for subsequent
CC refolding by other chaperones, such as HSPA8/HSC70. Does not refold
CC proteins by itself. Binding to cell surface receptors triggers
CC internalization of the chaperone-client complex and subsequent
CC lysosomal or proteasomal degradation. When secreted, protects cells
CC against apoptosis and against cytolysis by complement. Intracellular
CC forms interact with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3
CC ubiquitin-protein ligase complexes and promote the ubiquitination and
CC subsequent proteasomal degradation of target proteins. Promotes
CC proteasomal degradation of COMMD1 and IKBKB. Modulates NF-kappa-B
CC transcriptional activity (By similarity). Following stress, promotes
CC apoptosis (PubMed:12551933). Inhibits apoptosis when associated with
CC the mitochondrial membrane by interference with BAX-dependent release
CC of cytochrome c into the cytoplasm. Plays a role in the regulation of
CC cell proliferation. Following ER stress, suppresses stress-induced
CC apoptosis by stabilizing mitochondrial membrane integrity through
CC interaction with HSPA5. When secreted, does not affect caspase or BAX-
CC mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (By
CC similarity). When secreted, acts as an important modulator during
CC neuronal differentiation through interaction with STMN3 (By
CC similarity). Plays a role in the clearance of immune complexes that
CC arise during cell injury (PubMed:11865066).
CC {ECO:0000250|UniProtKB:P05371, ECO:0000250|UniProtKB:P10909,
CC ECO:0000269|PubMed:11865066, ECO:0000269|PubMed:12551933,
CC ECO:0000269|PubMed:14741101}.
CC -!- SUBUNIT: Antiparallel disulfide-linked heterodimer of an alpha chain
CC and a beta chain. Self-associates and forms higher oligomers. Interacts
CC with a broad range of misfolded proteins, including APP, APOC2 and LYZ.
CC Slightly acidic pH promotes interaction with misfolded proteins. Forms
CC high-molecular weight oligomers upon interaction with misfolded
CC proteins. Interacts with APOA1, LRP2, CLUAP1 and PON1. Interacts with
CC the complement complex (By similarity). Interacts (via alpha chain)
CC with XRCC6 (PubMed:12551933). Interacts with SYVN1, COMMD1, BTRC, CUL1
CC and with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-
CC protein ligase complexes. Interacts (via alpha chain) with BAX in
CC stressed cells, where BAX undergoes a conformation change leading to
CC association with the mitochondrial membrane. Does not interact with BAX
CC in unstressed cells. Found in a complex with LTF, CLU, EPPIN and SEMG1.
CC Interacts (immaturely glycosylated pre-secreted form) with HSPA5; this
CC interaction promotes CLU stability and facilitates stress-induced CLU
CC retrotranslocation from the secretory pathway to the mitochondria,
CC thereby reducing stress-induced apoptosis by stabilizing mitochondrial
CC membrane integrity. Interacts with BCL2L1; this interaction releases
CC and activates BAX and promotes cell death. Interacts with TGFBR2 and
CC ACVR1 (By similarity). Interacts (secreted form) with STMN3; this
CC interaction may act as an important modulator during neuronal
CC differentiation (By similarity). Interacts with VLDLR and LRP8 (By
CC similarity). {ECO:0000250|UniProtKB:P05371,
CC ECO:0000250|UniProtKB:P10909, ECO:0000269|PubMed:12551933}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12551933}. Nucleus
CC {ECO:0000269|PubMed:12551933}. Cytoplasm {ECO:0000269|PubMed:12551933}.
CC Mitochondrion membrane {ECO:0000250|UniProtKB:P10909}; Peripheral
CC membrane protein {ECO:0000250|UniProtKB:P10909}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P10909}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:12551933}. Microsome
CC {ECO:0000250|UniProtKB:P10909}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P10909}. Mitochondrion
CC {ECO:0000250|UniProtKB:P10909}. Mitochondrion membrane
CC {ECO:0000250|UniProtKB:P10909}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P05371}. Cytoplasmic vesicle, secretory vesicle,
CC chromaffin granule {ECO:0000250|UniProtKB:P10909}. Note=Can
CC retrotranslocate from the secretory compartments to the cytosol upon
CC cellular stress. Detected in perinuclear foci that may be aggresomes
CC containing misfolded, ubiquitinated proteins. Detected at the
CC mitochondrion membrane upon induction of apoptosis. Under ER stress, a
CC immaturely glycosylated pre-secreted form retrotranslocates from the
CC endoplasmic reticulum (ER)-Golgi network to the cytoplasm to localize
CC in the mitochondria through HSPA5 interaction. ER stress reduces
CC secretion. Under the stress, minor amounts of non-secreted forms
CC accumulate in cytoplasm. {ECO:0000250|UniProtKB:P10909}.
CC -!- TISSUE SPECIFICITY: Most abundant in stomach, liver, brain, and testis,
CC with intermediate levels in heart, ovary and kidney.
CC -!- PTM: Proteolytically cleaved on its way through the secretory system,
CC probably within the Golgi lumen. Proteolytic cleavage is not necessary
CC for its chaperone activity. All non-secreted forms are not
CC proteolytically cleaved. Chaperone activity of uncleaved forms is
CC dependent on a non-reducing environment.
CC {ECO:0000250|UniProtKB:P10909}.
CC -!- PTM: Polyubiquitinated, leading to proteasomal degradation. Under
CC cellular stress, the intracellular level of cleaved form is reduced due
CC to proteasomal degradation. {ECO:0000250|UniProtKB:P10909}.
CC -!- PTM: Extensively glycosylated with sulfated N-linked carbohydrates (By
CC similarity). About 30% of the protein mass is comprised of complex N-
CC linked carbohydrate. Endoplasmic reticulum (ER) stress induces changes
CC in glycosylation status and increases level of hypoglycosylated forms.
CC Core carbohydrates are essential for chaperone activity. Non-secreted
CC forms are hypoglycosylated or unglycosylated (By similarity).
CC {ECO:0000250|UniProtKB:P10909}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype (PubMed:11067863,
CC PubMed:11865066). During myocarditis, mice show an increased tendency
CC to cardiac tissue injury (PubMed:11067863). Homozygous CLU aging mice
CC exhibit a striking glomerulopathy characterized by progressive
CC mesangial expansion and collapse of capillary lumens (PubMed:11865066).
CC {ECO:0000269|PubMed:11067863, ECO:0000269|PubMed:11865066}.
CC -!- SIMILARITY: Belongs to the clusterin family. {ECO:0000305}.
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DR EMBL; D14077; BAA03162.1; -; mRNA.
DR EMBL; L08235; AAA37422.1; -; mRNA.
DR EMBL; S70244; AAB30623.1; -; mRNA.
DR EMBL; L05670; AAA37284.1; -; mRNA.
DR EMBL; BC075668; AAH75668.1; -; mRNA.
DR CCDS; CCDS36957.1; -.
DR PIR; A40714; A40714.
DR PIR; I56335; I56335.
DR RefSeq; NP_038520.2; NM_013492.3.
DR RefSeq; XP_006518567.1; XM_006518504.3.
DR AlphaFoldDB; Q06890; -.
DR SMR; Q06890; -.
DR BioGRID; 198760; 28.
DR IntAct; Q06890; 5.
DR MINT; Q06890; -.
DR STRING; 10090.ENSMUSP00000022616; -.
DR GlyConnect; 761; 5 N-Linked glycans (2 sites).
DR GlyGen; Q06890; 6 sites, 7 N-linked glycans (2 sites).
DR iPTMnet; Q06890; -.
DR PhosphoSitePlus; Q06890; -.
DR CPTAC; non-CPTAC-5592; -.
DR CPTAC; non-CPTAC-5593; -.
DR CPTAC; non-CPTAC-5594; -.
DR jPOST; Q06890; -.
DR PaxDb; Q06890; -.
DR PeptideAtlas; Q06890; -.
DR PRIDE; Q06890; -.
DR ProteomicsDB; 283529; -.
DR Antibodypedia; 631; 1266 antibodies from 51 providers.
DR DNASU; 12759; -.
DR Ensembl; ENSMUST00000022616; ENSMUSP00000022616; ENSMUSG00000022037.
DR GeneID; 12759; -.
DR KEGG; mmu:12759; -.
DR UCSC; uc007ujs.2; mouse.
DR CTD; 1191; -.
DR MGI; MGI:88423; Clu.
DR VEuPathDB; HostDB:ENSMUSG00000022037; -.
DR eggNOG; ENOG502RBQP; Eukaryota.
DR GeneTree; ENSGT00530000063668; -.
DR HOGENOM; CLU_042162_2_0_1; -.
DR InParanoid; Q06890; -.
DR OMA; QGSKYIN; -.
DR OrthoDB; 973835at2759; -.
DR PhylomeDB; Q06890; -.
DR TreeFam; TF333030; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR Reactome; R-MMU-166665; Terminal pathway of complement.
DR Reactome; R-MMU-6803157; Antimicrobial peptides.
DR Reactome; R-MMU-977606; Regulation of Complement cascade.
DR BioGRID-ORCS; 12759; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Clu; mouse.
DR PRO; PR:Q06890; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q06890; protein.
DR Bgee; ENSMUSG00000022037; Expressed in iris and 295 other tissues.
DR ExpressionAtlas; Q06890; baseline and differential.
DR Genevisible; Q06890; MM.
DR GO; GO:0016235; C:aggresome; ISO:MGI.
DR GO; GO:0097440; C:apical dendrite; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0071944; C:cell periphery; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0042583; C:chromaffin granule; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0030426; C:growth cone; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0097418; C:neurofibrillary tangle; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0099020; C:perinuclear endoplasmic reticulum lumen; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0034366; C:spherical high-density lipoprotein particle; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IDA:SynGO.
DR GO; GO:0001540; F:amyloid-beta binding; ISO:MGI.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; ISO:MGI.
DR GO; GO:0051787; F:misfolded protein binding; ISS:UniProtKB.
DR GO; GO:0140597; F:protein carrier chaperone; ISO:MGI.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0048156; F:tau protein binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISS:UniProtKB.
DR GO; GO:0051082; F:unfolded protein binding; ISS:UniProtKB.
DR GO; GO:0000902; P:cell morphogenesis; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0032286; P:central nervous system myelin maintenance; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0061077; P:chaperone-mediated protein folding; ISS:UniProtKB.
DR GO; GO:0031018; P:endocrine pancreas development; ISO:MGI.
DR GO; GO:0002434; P:immune complex clearance; IMP:UniProtKB.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0001774; P:microglial cell activation; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0061518; P:microglial cell proliferation; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:1905907; P:negative regulation of amyloid fibril formation; IMP:UniProtKB.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0060548; P:negative regulation of cell death; ISO:MGI.
DR GO; GO:1905892; P:negative regulation of cellular response to thapsigargin; ISO:MGI.
DR GO; GO:1905895; P:negative regulation of cellular response to tunicamycin; ISO:MGI.
DR GO; GO:1902230; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage; ISS:UniProtKB.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISS:UniProtKB.
DR GO; GO:1903573; P:negative regulation of response to endoplasmic reticulum stress; ISO:MGI.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISO:MGI.
DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; IMP:Alzheimers_University_of_Toronto.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:1902998; P:positive regulation of neurofibrillary tangle assembly; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:1901216; P:positive regulation of neuron death; IMP:Alzheimers_University_of_Toronto.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:MGI.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; ISS:UniProtKB.
DR GO; GO:1902949; P:positive regulation of tau-protein kinase activity; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0017038; P:protein import; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0061740; P:protein targeting to lysosome involved in chaperone-mediated autophagy; ISO:MGI.
DR GO; GO:1900221; P:regulation of amyloid-beta clearance; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:1901214; P:regulation of neuron death; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:1902847; P:regulation of neuronal signal transduction; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0051788; P:response to misfolded protein; ISS:UniProtKB.
DR GO; GO:0009615; P:response to virus; IEA:Ensembl.
DR InterPro; IPR016016; Clusterin.
DR InterPro; IPR000753; Clusterin-like.
DR InterPro; IPR016015; Clusterin_C.
DR InterPro; IPR033986; Clusterin_CS.
DR InterPro; IPR016014; Clusterin_N.
DR PANTHER; PTHR10970; PTHR10970; 1.
DR PANTHER; PTHR10970:SF1; PTHR10970:SF1; 1.
DR Pfam; PF01093; Clusterin; 1.
DR PIRSF; PIRSF002368; Clusterin; 1.
DR SMART; SM00035; CLa; 1.
DR SMART; SM00030; CLb; 1.
DR PROSITE; PS00492; CLUSTERIN_1; 1.
DR PROSITE; PS00493; CLUSTERIN_2; 1.
PE 1: Evidence at protein level;
KW Chaperone; Cytoplasm; Cytoplasmic vesicle; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Membrane; Microsome; Mitochondrion;
KW Nucleus; Phosphoprotein; Reference proteome; Secreted; Signal;
KW Ubl conjugation.
FT SIGNAL 1..21
FT /evidence="ECO:0000250"
FT CHAIN 22..448
FT /note="Clusterin"
FT /id="PRO_0000005535"
FT CHAIN 22..226
FT /note="Clusterin beta chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000005536"
FT CHAIN 227..447
FT /note="Clusterin alpha chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000005537"
FT MOTIF 77..80
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:12551933"
FT MOTIF 442..446
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:12551933"
FT MOD_RES 132
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10909"
FT MOD_RES 395
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10909"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT CARBOHYD 290
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17330941"
FT CARBOHYD 327
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT CARBOHYD 373
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT DISULFID 101..312
FT /note="Interchain (between beta and alpha chains)"
FT /evidence="ECO:0000250"
FT DISULFID 112..304
FT /note="Interchain (between beta and alpha chains)"
FT /evidence="ECO:0000250"
FT DISULFID 115..301
FT /note="Interchain (between beta and alpha chains)"
FT /evidence="ECO:0000250"
FT DISULFID 120..294
FT /note="Interchain (between beta and alpha chains)"
FT /evidence="ECO:0000250"
FT DISULFID 128..284
FT /note="Interchain (between beta and alpha chains)"
FT /evidence="ECO:0000250"
FT MUTAGEN 78..79
FT /note="KK->AV: Reduced nuclear location."
FT /evidence="ECO:0000269|PubMed:12551933"
FT MUTAGEN 343
FT /note="L->P: Abolishes interaction with XRCC6."
FT /evidence="ECO:0000269|PubMed:12551933"
FT MUTAGEN 357..358
FT /note="LL->RQ: Abolishes interaction with XRCC6."
FT /evidence="ECO:0000269|PubMed:12551933"
FT MUTAGEN 361
FT /note="L->R: Abolishes interaction with XRCC6."
FT /evidence="ECO:0000269|PubMed:12551933"
FT MUTAGEN 371
FT /note="L->R: Strongly reduced interaction with XRCC6."
FT /evidence="ECO:0000269|PubMed:12551933"
FT MUTAGEN 442..443
FT /note="RR->VV: Strongly reduced nuclear location."
FT /evidence="ECO:0000269|PubMed:12551933"
FT CONFLICT 10
FT /note="L -> M (in Ref. 3; AAB30623)"
FT /evidence="ECO:0000305"
FT CONFLICT 335..336
FT /note="RL -> TV (in Ref. 4; AAA37284)"
FT /evidence="ECO:0000305"
FT CONFLICT 350
FT /note="K -> N (in Ref. 4; AAA37284)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 448 AA; 51656 MW; A860600A6F8D47F6 CRC64;
MKILLLCVAL LLIWDNGMVL GEQEVSDNEL QELSTQGSRY INKEIQNAVQ GVKHIKTLIE
KTNAERKSLL NSLEEAKKKK EDALEDTRDS EMKLKAFPEV CNETMMALWE ECKPCLKHTC
MKFYARVCRS GSGLVGQQLE EFLNQSSPFY FWMNGDRIDS LLESDRQQSQ VLDAMQDSFA
RASGIIDTLF QDRFFARELH DPHYFSPIGF PHKRPHFLYP KSRLVRSLMS PSHYGPPSFH
NMFQPFFEMI HQAQQAMDVQ LHSPAFQFPD VDFLREGEDD RTVCKEIRRN STGCLKMKGQ
CEKCQEILSV DCSTNNPAQA NLRQELNDSL QVAERLTEQY KELLQSFQSK MLNTSSLLEQ
LNDQFNWVSQ LANLTQGEDK YYLRVSTVTT HSSDSEVPSR VTEVVVKLFD SDPITVVLPE
EVSKDNPKFM DTVAEKALQE YRRKSRAE
