Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P05371 (CLUS_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | 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):
Dimeric acid glycoprotein
Short name=DAG
Sulfated glycoprotein 2
Short name=SGP-2
Testosterone repressed prostate message 2
Short name=TRPM-2

Cleaved into the following 2 chains:

  1. Clusterin beta chain
  2. Clusterin alpha chain
Gene names
Name:Clu
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length447 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. Interacts (via alpha chain) with XRCC6 By similarity. Found in a complex with LTF, CLU, EPPIN and SEMG1 By similarity. Ref.4

Subcellular location

Secreted. Nucleus By similarity. Cytoplasm By similarity. Mitochondrion membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cytoplasmcytosol By similarity. 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.1 Ref.4

Tissue specificity

Detected in Sertoli cells (at protein level). Detected in cultured Sertoli cells, testis, epididymis, liver and brain. Ref.1

Developmental stage

Expressed by cells undergoing programmed death as a result of the hormonal stimuli or a traumatic insult.

Post-translational modification

Extensively glycosylated with sulfated N-linked carbohydrates. Ref.1

Proteolytically cleaved on its way through the secretory system, probably within the Golgi lumen By similarity. Ref.1 Ref.4

Polyubiquitinated, leading to proteasomal degradation By similarity.

Sequence similarities

Belongs to the clusterin family.

Ontologies

Keywords
   Biological processDifferentiation
Spermatogenesis
   Cellular componentCytoplasm
Cytoplasmic vesicle
Endoplasmic reticulum
Membrane
Microsome
Mitochondrion
Nucleus
Secreted
   DomainSignal
   Molecular functionChaperone
Developmental protein
   PTMDisulfide bond
Glycoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Traceable author statement Ref.3. Source: RGD

cellular response to growth factor stimulus

Inferred from expression pattern PubMed 16038898. Source: RGD

chaperone-mediated protein folding

Inferred from sequence or structural similarity. Source: UniProtKB

endocrine pancreas development

Inferred from mutant phenotype PubMed 16411126. Source: RGD

intrinsic apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 15591223. Source: RGD

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

neuron projection morphogenesis

Inferred from mutant phenotype PubMed 16038898. Source: RGD

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 cell differentiation

Inferred from mutant phenotype PubMed 16411126. Source: RGD

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 15591223. Source: RGD

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 oxidative stress

Inferred from expression pattern PubMed 14512294. Source: RGD

response to potassium ion

Inferred from expression pattern PubMed 12782389. Source: RGD

response to wounding

Inferred from expression pattern PubMed 12457227. Source: RGD

spermatogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentaggresome

Inferred from direct assay PubMed 12799419. Source: RGD

chromaffin 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 space

Inferred from sequence or structural similarity. Source: UniProtKB

growth cone

Inferred from direct assay PubMed 16038898. Source: RGD

mitochondrial membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

neuron projection

Inferred from direct assay PubMed 16038898. Source: RGD

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from direct assay PubMed 16038898. Source: RGD

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 Ref.1 Ref.4
Chain22 – 447426Clusterin
PRO_0000005544
Chain22 – 226205Clusterin beta chain
PRO_0000005545
Chain227 – 447221Clusterin alpha chain
PRO_0000005546

Regions

Motif77 – 804Nuclear localization signal By similarity
Motif441 – 4455Nuclear localization signal By similarity

Amino acid modifications

Glycosylation1021N-linked (GlcNAc...) Probable
Glycosylation1441N-linked (GlcNAc...) Probable
Glycosylation2901N-linked (GlcNAc...) Probable
Glycosylation3271N-linked (GlcNAc...) Probable
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

Sequence conflict1871D → H in AAA41273. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P05371 [UniParc].

Last modified February 1, 1994. Version 2.
Checksum: 9E2FA33E5E0C146E

FASTA44751,375
        10         20         30         40         50         60 
MKILLLCVAL LLTWDNGMVL GEQEFSDNEL QELSTQGSRY VNKEIQNAVQ GVKHIKTLIE 

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

       130        140        150        160        170        180 
MKFYARVCRS GSGLVGRQLE EFLNQSSPFY FWMNGDRIDS LLESDRQQSQ VLDAMQDSFT 

       190        200        210        220        230        240 
RASGIIDTLF QDRFFTHEPQ DIHHFSPMGF PHKRPHFLYP KSRLVRSLMP LSHYGPLSFH 

       250        260        270        280        290        300 
NMFQPFFDMI HQAQQAMDVQ LHSPALQFPD VDFLKEGEDD PTVCKEIRHN STGCLKMKGQ 

       310        320        330        340        350        360 
CEKCQEILSV DCSTNNPAQA NLRQELNDSL QVAERLTQQY NELLHSLQSK MLNTSSLLEQ 

       370        380        390        400        410        420 
LNDQFTWVSQ LANLTQGDDQ YLRVSTVTTH SSDSEVPSRV TEVVVKLFDS DPITVVLPEE 

       430        440 
VSKDNPKFMD TVAEKALQEY RRKSRME 

« Hide

References

[1]"Biosynthesis and molecular cloning of sulfated glycoprotein 2 secreted by rat Sertoli cells."
Collard M.W., Griswold M.D.
Biochemistry 26:3297-3303(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 22-45 AND 227-241, PROTEOLYTIC PROCESSING, GLYCOSYLATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]"Identification of an androgen-repressed mRNA in rat ventral prostate as coding for sulphated glycoprotein 2 by cDNA cloning and sequence analysis."
Bettuzzi S., Hiipakka R.A., Gilna P., Liao S.
Biochem. J. 257:293-296(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Prostate.
[3]"Genomic organization and expression of the rat TRPM-2 (clusterin) gene, a gene implicated in apoptosis."
Wong P., Pineault J.M., Lakins J., Taillefer D., Leger J., Wang C., Tenniswood M.
J. Biol. Chem. 268:5021-5031(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
Strain: Sprague-Dawley.
[4]"Rat clusterin isolated from primary Sertoli cell-enriched culture medium is sulfated glycoprotein-2 (SGP-2)."
Cheng C.Y., Chen C.C., Feng Z., Marshall A., Bardin C.W.
Biochem. Biophys. Res. Commun. 155:398-404(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 22-51 AND 227-256, SUBCELLULAR LOCATION, SUBUNIT, PROTEOLYTIC PROCESSING.
[5]"Characterization of the products of a gene expressed during androgen-programmed cell death and their potential use as a marker of urogenital injury."
Bandyk M.G., Sawczuk I.S., Olsson C.A., Katz A.E., Buttyan R.
J. Urol. 143:407-413(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF TRPM-2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M16975 mRNA. Translation: AAA41273.1.
X13231 mRNA. Translation: CAA31618.1.
M64723 mRNA. Translation: AAA42298.1.
M64733 Genomic DNA. Translation: AAA42299.1.
PIRA27205. A45890.
RefSeqNP_444180.2. NM_053021.2.
UniGeneRn.1780.

3D structure databases

DisProtDP00014.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP05371. 1 interaction.
MINTMINT-4586114.

Proteomic databases

PaxDbP05371.
PRIDEP05371.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID24854.
KEGGrno:24854.
UCSCRGD:3907. rat.

Organism-specific databases

CTD1191.
RGD3907. Clu.

Phylogenomic databases

eggNOGNOG26650.
HOGENOMHOG000111799.
HOVERGENHBG006908.
InParanoidP05371.
KOK17252.
PhylomeDBP05371.

Gene expression databases

GenevestigatorP05371.

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

NextBio604646.
PROP05371.

Entry information

Entry nameCLUS_RAT
AccessionPrimary (citable) accession number: P05371
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: February 1, 1994
Last modified: April 16, 2014
This is version 111 of the entry and version 2 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