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Protein

Clusterin

Gene

Clu

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionChaperone

Enzyme and pathway databases

ReactomeiR-MMU-114608 Platelet degranulation
R-MMU-166665 Terminal pathway of complement
R-MMU-6803157 Antimicrobial peptides
R-MMU-977606 Regulation of Complement cascade

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:88423 Clu

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
Mutagenesisi78 – 79KK → AV: Reduced nuclear location. 1 Publication2
Mutagenesisi343L → P: Abolishes interaction with XRCC6. 1 Publication1
Mutagenesisi357 – 358LL → RQ: Abolishes interaction with XRCC6. 1 Publication2
Mutagenesisi361L → R: Abolishes interaction with XRCC6. 1 Publication1
Mutagenesisi371L → R: Strongly reduced interaction with XRCC6. 1 Publication1
Mutagenesisi442 – 443RR → VV: Strongly reduced nuclear location. 1 Publication2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21By similarityAdd BLAST21
ChainiPRO_000000553522 – 448ClusterinAdd BLAST427
ChainiPRO_000000553622 – 226Clusterin beta chainBy similarityAdd BLAST205
ChainiPRO_0000005537227 – 447Clusterin alpha chainBy similarityAdd BLAST221

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi101 ↔ 312Interchain (between beta and alpha chains)By similarity
Glycosylationi102N-linked (GlcNAc...) asparagineCurated1
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 residuei132PhosphoserineBy similarity1
Glycosylationi144N-linked (GlcNAc...) asparagineCurated1
Glycosylationi290N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi327N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi353N-linked (GlcNAc...) asparagineCurated1
Glycosylationi373N-linked (GlcNAc...) asparagineCurated1
Modified residuei395PhosphoserineBy similarity1

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

PaxDbiQ06890
PeptideAtlasiQ06890
PRIDEiQ06890

PTM databases

GlyConnecti761
iPTMnetiQ06890
PhosphoSitePlusiQ06890

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSMUSG00000022037
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi19876010 interactors.
IntActiQ06890 8 interactors.
MINTiQ06890
STRINGi10090.ENSMUSP00000022616

Structurei

3D structure databases

ProteinModelPortaliQ06890
SMRiQ06890
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi77 – 80Nuclear localization signal4
Motifi442 – 446Nuclear localization signal5

Sequence similaritiesi

Belongs to the clusterin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IHRB Eukaryota
ENOG410YYKB LUCA
GeneTreeiENSGT00530000063668
HOGENOMiHOG000111799
HOVERGENiHBG006908
InParanoidiQ06890
KOiK17252
OMAiMKFYARV
OrthoDBiEOG091G05R5
PhylomeDBiQ06890
TreeFamiTF333030

Family and domain databases

InterProiView protein in InterPro
IPR016016 Clusterin
IPR000753 Clusterin-like
IPR016015 Clusterin_C
IPR033986 Clusterin_CS
IPR016014 Clusterin_N
PANTHERiPTHR10970 PTHR10970, 1 hit
PTHR10970:SF1 PTHR10970:SF1, 1 hit
PfamiView protein in Pfam
PF01093 Clusterin, 1 hit
PIRSFiPIRSF002368 Clusterin, 1 hit
SMARTiView protein in SMART
SM00035 CLa, 1 hit
SM00030 CLb, 1 hit
PROSITEiView protein in PROSITE
PS00492 CLUSTERIN_1, 1 hit
PS00493 CLUSTERIN_2, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti10L → M in AAB30623 (PubMed:8169523).Curated1
Sequence conflicti335 – 336RL → TV in AAA37284 (Ref. 4) Curated2
Sequence conflicti350K → N in AAA37284 (Ref. 4) Curated1

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_013492.3
XP_006518567.1, XM_006518504.3
UniGeneiMm.200608

Genome annotation databases

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

Similar proteinsi

Entry informationi

Entry nameiCLUS_MOUSE
AccessioniPrimary (citable) accession number: Q06890
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: April 25, 2018
This is version 159 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome