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P05371

- CLUS_RAT

UniProt

P05371 - CLUS_RAT

Protein

Clusterin

Gene

Clu

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 114 (01 Oct 2014)
      Sequence version 2 (01 Feb 1994)
      Previous versions | rss
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    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

    1. misfolded protein binding Source: UniProtKB
    2. protein binding Source: RGD
    3. ubiquitin protein ligase binding Source: UniProtKB

    GO - Biological processi

    1. apoptotic process Source: RGD
    2. cell morphogenesis Source: Alzheimers_University_of_Toronto
    3. cellular response to growth factor stimulus Source: RGD
    4. central nervous system myelin maintenance Source: Alzheimers_University_of_Toronto
    5. chaperone-mediated protein complex assembly Source: Alzheimers_University_of_Toronto
    6. chaperone-mediated protein folding Source: UniProtKB
    7. endocrine pancreas development Source: RGD
    8. intrinsic apoptotic signaling pathway Source: UniProtKB
    9. microglial cell activation Source: Alzheimers_University_of_Toronto
    10. microglial cell proliferation Source: Alzheimers_University_of_Toronto
    11. negative regulation of apoptotic process Source: RGD
    12. negative regulation of beta-amyloid formation Source: Alzheimers_University_of_Toronto
    13. negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage Source: BHF-UCL
    14. negative regulation of protein homooligomerization Source: UniProtKB
    15. neuron projection morphogenesis Source: RGD
    16. positive regulation of apoptotic process Source: UniProtKB
    17. positive regulation of beta-amyloid formation Source: Alzheimers_University_of_Toronto
    18. positive regulation of cell differentiation Source: RGD
    19. positive regulation of cell proliferation Source: RGD
    20. positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
    21. positive regulation of neurofibrillary tangle assembly Source: Alzheimers_University_of_Toronto
    22. positive regulation of neuron death Source: Alzheimers_University_of_Toronto
    23. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
    24. positive regulation of nitric oxide biosynthetic process Source: Alzheimers_University_of_Toronto
    25. positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
    26. positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: UniProtKB
    27. positive regulation of tau-protein kinase activity Source: Alzheimers_University_of_Toronto
    28. positive regulation of tumor necrosis factor production Source: Alzheimers_University_of_Toronto
    29. protein import Source: Alzheimers_University_of_Toronto
    30. protein stabilization Source: UniProtKB
    31. regulation of beta-amyloid clearance Source: Alzheimers_University_of_Toronto
    32. regulation of neuronal signal transduction Source: Alzheimers_University_of_Toronto
    33. regulation of neuron death Source: Alzheimers_University_of_Toronto
    34. response to misfolded protein Source: UniProtKB
    35. response to oxidative stress Source: RGD
    36. response to potassium ion Source: RGD
    37. response to wounding Source: RGD
    38. spermatogenesis Source: UniProtKB-KW

    Keywords - Molecular functioni

    Chaperone, Developmental protein

    Keywords - Biological processi

    Differentiation, Spermatogenesis

    Names & Taxonomyi

    Protein namesi
    Recommended 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:
    Gene namesi
    Name:Clu
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi3907. Clu.

    Subcellular locationi

    Secreted 2 Publications. Nucleus By similarity. Cytoplasm By similarity. Mitochondrion membrane By similarity; Peripheral membrane protein By similarity; 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.By similarity

    GO - Cellular componenti

    1. aggresome Source: RGD
    2. apical dendrite Source: Alzheimers_University_of_Toronto
    3. chromaffin granule Source: UniProtKB-SubCell
    4. cytoplasm Source: Alzheimers_University_of_Toronto
    5. cytosol Source: UniProtKB-SubCell
    6. endoplasmic reticulum Source: UniProtKB-SubCell
    7. extracellular space Source: UniProtKB
    8. growth cone Source: RGD
    9. mitochondrial membrane Source: UniProtKB-SubCell
    10. neurofibrillary tangle Source: Alzheimers_University_of_Toronto
    11. neuron projection Source: RGD
    12. nucleus Source: UniProtKB-SubCell
    13. perinuclear region of cytoplasm Source: RGD
    14. spherical high-density lipoprotein particle Source: UniProtKB

    Keywords - Cellular componenti

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

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 21212 PublicationsAdd
    BLAST
    Chaini22 – 447426ClusterinPRO_0000005544Add
    BLAST
    Chaini22 – 226205Clusterin beta chainPRO_0000005545Add
    BLAST
    Chaini227 – 447221Clusterin alpha chainPRO_0000005546Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi101 ↔ 312Interchain (between beta and alpha chains)By similarity
    Glycosylationi102 – 1021N-linked (GlcNAc...)1 Publication
    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
    Glycosylationi144 – 1441N-linked (GlcNAc...)1 Publication
    Glycosylationi290 – 2901N-linked (GlcNAc...)1 Publication
    Glycosylationi327 – 3271N-linked (GlcNAc...)1 Publication
    Glycosylationi353 – 3531N-linked (GlcNAc...)1 Publication
    Glycosylationi373 – 3731N-linked (GlcNAc...)1 Publication

    Post-translational modificationi

    Extensively glycosylated with sulfated N-linked carbohydrates.1 Publication
    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, Ubl conjugation

    Proteomic databases

    PaxDbiP05371.
    PRIDEiP05371.

    Expressioni

    Tissue specificityi

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

    Developmental stagei

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

    Gene expression databases

    GenevestigatoriP05371.

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

    Protein-protein interaction databases

    IntActiP05371. 1 interaction.
    MINTiMINT-4586114.

    Structurei

    3D structure databases

    DisProtiDP00014.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi77 – 804Nuclear localization signalBy similarity
    Motifi441 – 4455Nuclear localization signalBy similarity

    Sequence similaritiesi

    Belongs to the clusterin family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG26650.
    HOGENOMiHOG000111799.
    HOVERGENiHBG006908.
    InParanoidiP05371.
    KOiK17252.
    PhylomeDBiP05371.

    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.

    P05371-1 [UniParc]FASTAAdd to Basket

    « Hide

    MKILLLCVAL LLTWDNGMVL GEQEFSDNEL QELSTQGSRY VNKEIQNAVQ    50
    GVKHIKTLIE KTNAERKSLL NSLEEAKKKK EGALDDTRDS EMKLKAFPEV 100
    CNETMMALWE ECKPCLKHTC MKFYARVCRS GSGLVGRQLE EFLNQSSPFY 150
    FWMNGDRIDS LLESDRQQSQ VLDAMQDSFT RASGIIDTLF QDRFFTHEPQ 200
    DIHHFSPMGF PHKRPHFLYP KSRLVRSLMP LSHYGPLSFH NMFQPFFDMI 250
    HQAQQAMDVQ LHSPALQFPD VDFLKEGEDD PTVCKEIRHN STGCLKMKGQ 300
    CEKCQEILSV DCSTNNPAQA NLRQELNDSL QVAERLTQQY NELLHSLQSK 350
    MLNTSSLLEQ LNDQFTWVSQ LANLTQGDDQ YLRVSTVTTH SSDSEVPSRV 400
    TEVVVKLFDS DPITVVLPEE VSKDNPKFMD TVAEKALQEY RRKSRME 447
    Length:447
    Mass (Da):51,375
    Last modified:February 1, 1994 - v2
    Checksum:i9E2FA33E5E0C146E
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti187 – 1871D → H in AAA41273. (PubMed:3651384)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M16975 mRNA. Translation: AAA41273.1.
    X13231 mRNA. Translation: CAA31618.1.
    M64723 mRNA. Translation: AAA42298.1.
    M64733 Genomic DNA. Translation: AAA42299.1.
    PIRiA45890. A27205.
    RefSeqiNP_444180.2. NM_053021.2.
    UniGeneiRn.1780.

    Genome annotation databases

    GeneIDi24854.
    KEGGirno:24854.
    UCSCiRGD:3907. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M16975 mRNA. Translation: AAA41273.1 .
    X13231 mRNA. Translation: CAA31618.1 .
    M64723 mRNA. Translation: AAA42298.1 .
    M64733 Genomic DNA. Translation: AAA42299.1 .
    PIRi A45890. A27205.
    RefSeqi NP_444180.2. NM_053021.2.
    UniGenei Rn.1780.

    3D structure databases

    DisProti DP00014.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P05371. 1 interaction.
    MINTi MINT-4586114.

    Proteomic databases

    PaxDbi P05371.
    PRIDEi P05371.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 24854.
    KEGGi rno:24854.
    UCSCi RGD:3907. rat.

    Organism-specific databases

    CTDi 1191.
    RGDi 3907. Clu.

    Phylogenomic databases

    eggNOGi NOG26650.
    HOGENOMi HOG000111799.
    HOVERGENi HBG006908.
    InParanoidi P05371.
    KOi K17252.
    PhylomeDBi P05371.

    Miscellaneous databases

    NextBioi 604646.
    PROi P05371.

    Gene expression databases

    Genevestigatori P05371.

    Family and domain databases

    InterProi IPR016016. Clusterin.
    IPR000753. Clusterin-like.
    IPR016015. Clusterin_C.
    IPR016014. Clusterin_N.
    [Graphical view ]
    PANTHERi PTHR10970:SF1. PTHR10970:SF1. 1 hit.
    Pfami PF01093. Clusterin. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF002368. Clusterin. 1 hit.
    SMARTi SM00035. CLa. 1 hit.
    SM00030. CLb. 1 hit.
    [Graphical view ]
    PROSITEi PS00492. CLUSTERIN_1. 1 hit.
    PS00493. CLUSTERIN_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.

    Entry informationi

    Entry nameiCLUS_RAT
    AccessioniPrimary (citable) accession number: P05371
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1988
    Last sequence update: February 1, 1994
    Last modified: October 1, 2014
    This is version 114 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3