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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

ReactomeiR-MMU-114608. Platelet degranulation.
R-MMU-166665. Terminal pathway of complement.
R-MMU-6803157. Antimicrobial peptides.

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
Proteomesi
  • UP000000589 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)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...)Curated1
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...)Curated1
Glycosylationi290N-linked (GlcNAc...)1 Publication1
Glycosylationi327N-linked (GlcNAc...)1 Publication1
Glycosylationi353N-linked (GlcNAc...)Curated1
Glycosylationi373N-linked (GlcNAc...)Curated1
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

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

BioGridi198760. 6 interactors.
IntActiQ06890. 5 interactors.
MINTiMINT-1176977.
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

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)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.

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

3D structure databases

ProteinModelPortaliQ06890.
SMRiQ06890.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198760. 6 interactors.
IntActiQ06890. 5 interactors.
MINTiMINT-1176977.
STRINGi10090.ENSMUSP00000022616.

PTM databases

iPTMnetiQ06890.
PhosphoSitePlusiQ06890.

Proteomic databases

PaxDbiQ06890.
PeptideAtlasiQ06890.
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

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

Enzyme and pathway databases

ReactomeiR-MMU-114608. Platelet degranulation.
R-MMU-166665. Terminal pathway of complement.
R-MMU-6803157. Antimicrobial peptides.

Miscellaneous databases

ChiTaRSiClu. mouse.
PROiQ06890.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000022037.
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...

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: November 30, 2016
This is version 143 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

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 one 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.