Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Clusterin

Gene

Clu

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chaperone

Enzyme and pathway databases

ReactomeiREACT_307071. Platelet degranulation.

Names & Taxonomyi

Protein namesi
Recommended name:
Clusterin
Alternative name(s):
Apolipoprotein J
Short name:
Apo-J
Clustrin
Sulfated glycoprotein 2
Short name:
SGP-2
Cleaved into the following 2 chains:
Gene namesi
Name:Clu
Synonyms:Apoj, Msgp-2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:88423. Clu.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle, Endoplasmic reticulum, Membrane, Microsome, Mitochondrion, Nucleus, Secreted

Pathology & Biotechi

Disruption phenotypei

No visible phenotype. During myocarditis, mice show an increased tendency to cardiac tissue injury.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi78 – 792KK → AV: Reduced nuclear location. 1 Publication
Mutagenesisi343 – 3431L → P: Abolishes interaction with XRCC6. 1 Publication
Mutagenesisi357 – 3582LL → RQ: Abolishes interaction with XRCC6. 1 Publication
Mutagenesisi361 – 3611L → R: Abolishes interaction with XRCC6. 1 Publication
Mutagenesisi371 – 3711L → R: Strongly reduced interaction with XRCC6. 1 Publication
Mutagenesisi442 – 4432RR → VV: Strongly reduced nuclear location. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121By similarityAdd
BLAST
Chaini22 – 448427ClusterinPRO_0000005535Add
BLAST
Chaini22 – 226205Clusterin beta chainBy similarityPRO_0000005536Add
BLAST
Chaini227 – 447221Clusterin alpha chainBy similarityPRO_0000005537Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi101 ↔ 312Interchain (between beta and alpha chains)By similarity
Glycosylationi102 – 1021N-linked (GlcNAc...)Curated
Disulfide bondi112 ↔ 304Interchain (between beta and alpha chains)By similarity
Disulfide bondi115 ↔ 301Interchain (between beta and alpha chains)By similarity
Disulfide bondi120 ↔ 294Interchain (between beta and alpha chains)By similarity
Disulfide bondi128 ↔ 284Interchain (between beta and alpha chains)By similarity
Modified residuei132 – 1321PhosphoserineBy similarity
Glycosylationi144 – 1441N-linked (GlcNAc...)Curated
Glycosylationi290 – 2901N-linked (GlcNAc...)1 Publication
Glycosylationi327 – 3271N-linked (GlcNAc...)1 Publication
Glycosylationi353 – 3531N-linked (GlcNAc...)Curated
Glycosylationi373 – 3731N-linked (GlcNAc...)Curated
Modified residuei395 – 3951PhosphoserineBy similarity

Post-translational modificationi

Extensively glycosylated with sulfated N-linked carbohydrates.2 Publications
Proteolytically cleaved on its way through the secretory system, probably within the Golgi lumen.By similarity
Polyubiquitinated, leading to proteasomal degradation.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ06890.
PaxDbiQ06890.
PRIDEiQ06890.

PTM databases

PhosphoSiteiQ06890.

Expressioni

Tissue specificityi

Most abundant in stomach, liver, brain, and testis, with intermediate levels in heart, ovary and kidney.

Gene expression databases

BgeeiQ06890.
CleanExiMM_CLU.
ExpressionAtlasiQ06890. baseline and differential.
GenevisibleiQ06890. MM.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi198760. 3 interactions.
IntActiQ06890. 5 interactions.
MINTiMINT-1176977.
STRINGi10090.ENSMUSP00000022616.

Structurei

3D structure databases

ProteinModelPortaliQ06890.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi77 – 804Nuclear localization signal
Motifi442 – 4465Nuclear localization signal

Sequence similaritiesi

Belongs to the clusterin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG26650.
GeneTreeiENSGT00530000063668.
HOGENOMiHOG000111799.
HOVERGENiHBG006908.
InParanoidiQ06890.
KOiK17252.
OMAiMKFYARV.
OrthoDBiEOG7K6PV4.
PhylomeDBiQ06890.
TreeFamiTF333030.

Family and domain databases

InterProiIPR016016. Clusterin.
IPR000753. Clusterin-like.
IPR016015. Clusterin_C.
IPR016014. Clusterin_N.
[Graphical view]
PANTHERiPTHR10970:SF1. PTHR10970:SF1. 1 hit.
PfamiPF01093. Clusterin. 1 hit.
[Graphical view]
PIRSFiPIRSF002368. Clusterin. 1 hit.
SMARTiSM00035. CLa. 1 hit.
SM00030. CLb. 1 hit.
[Graphical view]
PROSITEiPS00492. CLUSTERIN_1. 1 hit.
PS00493. CLUSTERIN_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q06890-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKILLLCVAL LLIWDNGMVL GEQEVSDNEL QELSTQGSRY INKEIQNAVQ
60 70 80 90 100
GVKHIKTLIE KTNAERKSLL NSLEEAKKKK EDALEDTRDS EMKLKAFPEV
110 120 130 140 150
CNETMMALWE ECKPCLKHTC MKFYARVCRS GSGLVGQQLE EFLNQSSPFY
160 170 180 190 200
FWMNGDRIDS LLESDRQQSQ VLDAMQDSFA RASGIIDTLF QDRFFARELH
210 220 230 240 250
DPHYFSPIGF PHKRPHFLYP KSRLVRSLMS PSHYGPPSFH NMFQPFFEMI
260 270 280 290 300
HQAQQAMDVQ LHSPAFQFPD VDFLREGEDD RTVCKEIRRN STGCLKMKGQ
310 320 330 340 350
CEKCQEILSV DCSTNNPAQA NLRQELNDSL QVAERLTEQY KELLQSFQSK
360 370 380 390 400
MLNTSSLLEQ LNDQFNWVSQ LANLTQGEDK YYLRVSTVTT HSSDSEVPSR
410 420 430 440
VTEVVVKLFD SDPITVVLPE EVSKDNPKFM DTVAEKALQE YRRKSRAE
Length:448
Mass (Da):51,656
Last modified:February 1, 1995 - v1
Checksum:iA860600A6F8D47F6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti10 – 101L → M in AAB30623 (PubMed:8169523).Curated
Sequence conflicti335 – 3362RL → TV in AAA37284 (Ref. 4) Curated
Sequence conflicti350 – 3501K → N in AAA37284 (Ref. 4) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D14077 mRNA. Translation: BAA03162.1.
L08235 mRNA. Translation: AAA37422.1.
S70244 mRNA. Translation: AAB30623.1.
L05670 mRNA. Translation: AAA37284.1.
BC075668 mRNA. Translation: AAH75668.1.
CCDSiCCDS36957.1.
PIRiA40714.
I56335.
RefSeqiNP_038520.2. NM_013492.2.
XP_006518567.1. XM_006518504.2.
UniGeneiMm.200608.

Genome annotation databases

EnsembliENSMUST00000022616; ENSMUSP00000022616; ENSMUSG00000022037.
GeneIDi12759.
KEGGimmu:12759.
UCSCiuc007ujs.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D14077 mRNA. Translation: BAA03162.1.
L08235 mRNA. Translation: AAA37422.1.
S70244 mRNA. Translation: AAB30623.1.
L05670 mRNA. Translation: AAA37284.1.
BC075668 mRNA. Translation: AAH75668.1.
CCDSiCCDS36957.1.
PIRiA40714.
I56335.
RefSeqiNP_038520.2. NM_013492.2.
XP_006518567.1. XM_006518504.2.
UniGeneiMm.200608.

3D structure databases

ProteinModelPortaliQ06890.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198760. 3 interactions.
IntActiQ06890. 5 interactions.
MINTiMINT-1176977.
STRINGi10090.ENSMUSP00000022616.

PTM databases

PhosphoSiteiQ06890.

Proteomic databases

MaxQBiQ06890.
PaxDbiQ06890.
PRIDEiQ06890.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000022616; ENSMUSP00000022616; ENSMUSG00000022037.
GeneIDi12759.
KEGGimmu:12759.
UCSCiuc007ujs.2. mouse.

Organism-specific databases

CTDi1191.
MGIiMGI:88423. Clu.

Phylogenomic databases

eggNOGiNOG26650.
GeneTreeiENSGT00530000063668.
HOGENOMiHOG000111799.
HOVERGENiHBG006908.
InParanoidiQ06890.
KOiK17252.
OMAiMKFYARV.
OrthoDBiEOG7K6PV4.
PhylomeDBiQ06890.
TreeFamiTF333030.

Enzyme and pathway databases

ReactomeiREACT_307071. Platelet degranulation.

Miscellaneous databases

ChiTaRSiClu. mouse.
NextBioi282108.
PROiQ06890.
SOURCEiSearch...

Gene expression databases

BgeeiQ06890.
CleanExiMM_CLU.
ExpressionAtlasiQ06890. baseline and differential.
GenevisibleiQ06890. MM.

Family and domain databases

InterProiIPR016016. Clusterin.
IPR000753. Clusterin-like.
IPR016015. Clusterin_C.
IPR016014. Clusterin_N.
[Graphical view]
PANTHERiPTHR10970:SF1. PTHR10970:SF1. 1 hit.
PfamiPF01093. Clusterin. 1 hit.
[Graphical view]
PIRSFiPIRSF002368. Clusterin. 1 hit.
SMARTiSM00035. CLa. 1 hit.
SM00030. CLb. 1 hit.
[Graphical view]
PROSITEiPS00492. CLUSTERIN_1. 1 hit.
PS00493. CLUSTERIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and sequencing of sulfated glycoprotein-2 cDNA from testis of mouse: implications of two different mRNAs of SGP-2."
    Lee K.-H., Ji Y.-M., Lim H.M., Lee S.-C., You K.-H.
    Biochem. Biophys. Res. Commun. 194:1175-1180(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Testis.
  2. "Murine clusterin: molecular cloning and mRNA localization of a gene associated with epithelial differentiation processes during embryogenesis."
    French L.E., Chonn A., Ducrest D., Baumann B., Belin D., Wohlwend A., Kiss J.Z., Sappino A.P., Tschopp J., Schifferli J.A.
    J. Cell Biol. 122:1119-1130(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: BALB/c.
    Tissue: Heart.
  3. "Mouse apolipoprotein J: characterization of a gene implicated in atherosclerosis."
    Jordan-Starck T.C., Lund S.D., Witte D.P., Aronow B.J., Ley C.A., Stuart W.D., Swertfeger D.K., Clayton L.R., Sells S.F., Paigen B.
    J. Lipid Res. 35:194-210(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6 X CBA.
    Tissue: Liver.
  4. "Secretion of sulfated glycoprotein (clustrin) accompanies cytodifferentiation and structural remodeling of mouse BC3H1 myogenic cells."
    Hodgdon B.A., Min B.H., Yan H., Farris J.A., Foster D.N., Strauch A.R.
    Submitted (NOV-1992) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6.
    Tissue: Eye.
  6. Cited for: DISRUPTION PHENOTYPE.
  7. "Synthesis and functional analyses of nuclear clusterin, a cell death protein."
    Leskov K.S., Klokov D.Y., Li J., Kinsella T.J., Boothman D.A.
    J. Biol. Chem. 278:11590-11600(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH XRCC6, SUBCELLULAR LOCATION, MUTAGENESIS OF 78-LYS-LYS-79; LEU-343; 357-LEU-LEU-358; LEU-361; LEU-371 AND 442-ARG-ARG-443.
  8. "Proteome-wide characterization of N-glycosylation events by diagonal chromatography."
    Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.
    J. Proteome Res. 5:2438-2447(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-327.
    Strain: C57BL/6.
    Tissue: Plasma.
  9. "Enhanced analysis of the mouse plasma proteome using cysteine-containing tryptic glycopeptides."
    Bernhard O.K., Kapp E.A., Simpson R.J.
    J. Proteome Res. 6:987-995(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-290.
    Strain: C57BL/6.
    Tissue: Plasma.

Entry informationi

Entry nameiCLUS_MOUSE
AccessioniPrimary (citable) accession number: Q06890
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: July 22, 2015
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.