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Q06890 (CLUS_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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:

  1. Clusterin beta chain
  2. Clusterin alpha chain
Gene names
Name:Clu
Synonyms:Apoj, Msgp-2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length448 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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.

Subunit structure

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. Ref.7

Subcellular location

Secreted. Nucleus. Cytoplasm. Mitochondrion membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cytoplasmcytosol. Microsome By similarity. Endoplasmic reticulum By similarity. Cytoplasmic vesiclesecretory vesiclechromaffin granule By similarity. 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. Ref.7

Tissue specificity

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

Post-translational modification

Extensively glycosylated with sulfated N-linked carbohydrates.

Proteolytically cleaved on its way through the secretory system, probably within the Golgi lumen By similarity.

Polyubiquitinated, leading to proteasomal degradation By similarity.

Disruption phenotype

No visible phenotype. During myocarditis, mice show an increased tendency to cardiac tissue injury. Ref.6

Sequence similarities

Belongs to the clusterin family.

Ontologies

Keywords
   Cellular componentCytoplasm
Cytoplasmic vesicle
Endoplasmic reticulum
Membrane
Microsome
Mitochondrion
Nucleus
Secreted
   DomainSignal
   Molecular functionChaperone
   PTMDisulfide bond
Glycoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processchaperone-mediated protein folding

Inferred from sequence or structural similarity. Source: UniProtKB

intrinsic apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of protein homooligomerization

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of intrinsic apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

protein stabilization

Inferred from sequence or structural similarity. Source: UniProtKB

response to misfolded protein

Inferred from sequence or structural similarity. Source: UniProtKB

response to virus

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentchromaffin granule

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Inferred from electronic annotation. Source: UniProtKB-SubCell

endoplasmic reticulum

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular matrix

Inferred from electronic annotation. Source: Ensembl

extracellular space

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrial membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

spherical high-density lipoprotein particle

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionmisfolded protein binding

Inferred from sequence or structural similarity. Source: UniProtKB

ubiquitin protein ligase binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 By similarity
Chain22 – 448427Clusterin
PRO_0000005535
Chain22 – 226205Clusterin beta chain By similarity
PRO_0000005536
Chain227 – 447221Clusterin alpha chain By similarity
PRO_0000005537

Regions

Motif77 – 804Nuclear localization signal
Motif442 – 4465Nuclear localization signal

Amino acid modifications

Glycosylation1021N-linked (GlcNAc...) Probable
Glycosylation1441N-linked (GlcNAc...) Probable
Glycosylation2901N-linked (GlcNAc...) Ref.9
Glycosylation3271N-linked (GlcNAc...) Ref.8
Glycosylation3531N-linked (GlcNAc...) Probable
Glycosylation3731N-linked (GlcNAc...) Probable
Disulfide bond101 ↔ 312Interchain (between beta and alpha chains) By similarity
Disulfide bond112 ↔ 304Interchain (between beta and alpha chains) By similarity
Disulfide bond115 ↔ 301Interchain (between beta and alpha chains) By similarity
Disulfide bond120 ↔ 294Interchain (between beta and alpha chains) By similarity
Disulfide bond128 ↔ 284Interchain (between beta and alpha chains) By similarity

Experimental info

Mutagenesis78 – 792KK → AV: Reduced nuclear location.
Mutagenesis3431L → P: Abolishes interaction with XRCC6. Ref.7
Mutagenesis357 – 3582LL → RQ: Abolishes interaction with XRCC6.
Mutagenesis3611L → R: Abolishes interaction with XRCC6. Ref.7
Mutagenesis3711L → R: Strongly reduced interaction with XRCC6. Ref.7
Mutagenesis442 – 4432RR → VV: Strongly reduced nuclear location.
Sequence conflict101L → M in AAB30623. Ref.3
Sequence conflict335 – 3362RL → TV in AAA37284. Ref.4
Sequence conflict3501K → N in AAA37284. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Q06890 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: A860600A6F8D47F6

FASTA44851,656
        10         20         30         40         50         60 
MKILLLCVAL LLIWDNGMVL GEQEVSDNEL QELSTQGSRY INKEIQNAVQ GVKHIKTLIE 

        70         80         90        100        110        120 
KTNAERKSLL NSLEEAKKKK EDALEDTRDS EMKLKAFPEV CNETMMALWE ECKPCLKHTC 

       130        140        150        160        170        180 
MKFYARVCRS GSGLVGQQLE EFLNQSSPFY FWMNGDRIDS LLESDRQQSQ VLDAMQDSFA 

       190        200        210        220        230        240 
RASGIIDTLF QDRFFARELH DPHYFSPIGF PHKRPHFLYP KSRLVRSLMS PSHYGPPSFH 

       250        260        270        280        290        300 
NMFQPFFEMI HQAQQAMDVQ LHSPAFQFPD VDFLREGEDD RTVCKEIRRN STGCLKMKGQ 

       310        320        330        340        350        360 
CEKCQEILSV DCSTNNPAQA NLRQELNDSL QVAERLTEQY KELLQSFQSK MLNTSSLLEQ 

       370        380        390        400        410        420 
LNDQFNWVSQ LANLTQGEDK YYLRVSTVTT HSSDSEVPSR VTEVVVKLFD SDPITVVLPE 

       430        440 
EVSKDNPKFM DTVAEKALQE YRRKSRAE 

« Hide

References

« Hide 'large scale' references
[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]"Apolipoprotein J/clusterin limits the severity of murine autoimmune myocarditis."
McLaughlin L., Zhu G., Mistry M., Ley-Ebert C., Stuart W.D., Florio C.J., Groen P.A., Witt S.A., Kimball T.R., Witte D.P., Harmony J.A., Aronow B.J.
J. Clin. Invest. 106:1105-1113(2000) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA40714.
I56335.
RefSeqNP_038520.2. NM_013492.2.
XP_006518567.1. XM_006518504.1.
UniGeneMm.200608.

3D structure databases

ProteinModelPortalQ06890.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198760. 3 interactions.
IntActQ06890. 5 interactions.
MINTMINT-1176977.

PTM databases

PhosphoSiteQ06890.

Proteomic databases

PaxDbQ06890.
PRIDEQ06890.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000022616; ENSMUSP00000022616; ENSMUSG00000022037.
GeneID12759.
KEGGmmu:12759.
UCSCuc007ujs.2. mouse.

Organism-specific databases

CTD1191.
MGIMGI:88423. Clu.

Phylogenomic databases

eggNOGNOG26650.
HOGENOMHOG000111799.
HOVERGENHBG006908.
InParanoidQ06890.
KOK17252.
OMAKFYARVC.
OrthoDBEOG7K6PV4.
PhylomeDBQ06890.
TreeFamTF333030.

Gene expression databases

ArrayExpressQ06890.
BgeeQ06890.
CleanExMM_CLU.
GenevestigatorQ06890.

Family and domain databases

InterProIPR016016. Clusterin.
IPR000753. Clusterin-like.
IPR016015. Clusterin_C.
IPR016014. Clusterin_N.
[Graphical view]
PANTHERPTHR10970:SF1. PTHR10970:SF1. 1 hit.
PfamPF01093. Clusterin. 1 hit.
[Graphical view]
PIRSFPIRSF002368. Clusterin. 1 hit.
SMARTSM00035. CLa. 1 hit.
SM00030. CLb. 1 hit.
[Graphical view]
PROSITEPS00492. CLUSTERIN_1. 1 hit.
PS00493. CLUSTERIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCLU. mouse.
NextBio282108.
PROQ06890.
SOURCESearch...

Entry information

Entry nameCLUS_MOUSE
AccessionPrimary (citable) accession number: Q06890
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: April 16, 2014
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot