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P05371

- CLUS_RAT

UniProt

P05371 - CLUS_RAT

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Protein

Clusterin

Gene

Clu

Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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

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

GO - Biological processi

  1. aging 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. estrous cycle Source: RGD
  9. intrinsic apoptotic signaling pathway Source: UniProtKB
  10. microglial cell activation Source: Alzheimers_University_of_Toronto
  11. microglial cell proliferation Source: Alzheimers_University_of_Toronto
  12. negative regulation of apoptotic process Source: RGD
  13. negative regulation of beta-amyloid formation Source: Alzheimers_University_of_Toronto
  14. negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage Source: BHF-UCL
  15. negative regulation of protein homooligomerization Source: UniProtKB
  16. neuron projection morphogenesis Source: RGD
  17. positive regulation of apoptotic process Source: UniProtKB
  18. positive regulation of beta-amyloid formation Source: Alzheimers_University_of_Toronto
  19. positive regulation of cell differentiation Source: RGD
  20. positive regulation of cell proliferation Source: RGD
  21. positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  22. positive regulation of neurofibrillary tangle assembly Source: Alzheimers_University_of_Toronto
  23. positive regulation of neuron death Source: Alzheimers_University_of_Toronto
  24. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  25. positive regulation of nitric oxide biosynthetic process Source: Alzheimers_University_of_Toronto
  26. positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
  27. positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: UniProtKB
  28. positive regulation of tau-protein kinase activity Source: Alzheimers_University_of_Toronto
  29. positive regulation of tumor necrosis factor production Source: Alzheimers_University_of_Toronto
  30. protein import Source: Alzheimers_University_of_Toronto
  31. protein stabilization Source: UniProtKB
  32. regulation of beta-amyloid clearance Source: Alzheimers_University_of_Toronto
  33. regulation of neuronal signal transduction Source: Alzheimers_University_of_Toronto
  34. regulation of neuron death Source: Alzheimers_University_of_Toronto
  35. response to light stimulus Source: RGD
  36. response to misfolded protein Source: UniProtKB
  37. response to oxidative stress Source: RGD
  38. response to potassium ion Source: RGD
  39. response to wounding Source: RGD
  40. spermatogenesis Source: UniProtKB-KW
Complete GO annotation...

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. cytoplasm Source: Alzheimers_University_of_Toronto
  4. cytoplasmic vesicle Source: UniProtKB-KW
  5. endoplasmic reticulum Source: UniProtKB-KW
  6. extracellular space Source: UniProtKB
  7. growth cone Source: RGD
  8. membrane Source: UniProtKB-KW
  9. mitochondrion Source: UniProtKB-KW
  10. neurofibrillary tangle Source: Alzheimers_University_of_Toronto
  11. neuron projection Source: RGD
  12. nucleus Source: RGD
  13. perinuclear region of cytoplasm Source: RGD
  14. spherical high-density lipoprotein particle Source: UniProtKB
Complete GO annotation...

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

        10         20         30         40         50
MKILLLCVAL LLTWDNGMVL GEQEFSDNEL QELSTQGSRY VNKEIQNAVQ
60 70 80 90 100
GVKHIKTLIE KTNAERKSLL NSLEEAKKKK EGALDDTRDS EMKLKAFPEV
110 120 130 140 150
CNETMMALWE ECKPCLKHTC MKFYARVCRS GSGLVGRQLE EFLNQSSPFY
160 170 180 190 200
FWMNGDRIDS LLESDRQQSQ VLDAMQDSFT RASGIIDTLF QDRFFTHEPQ
210 220 230 240 250
DIHHFSPMGF PHKRPHFLYP KSRLVRSLMP LSHYGPLSFH NMFQPFFDMI
260 270 280 290 300
HQAQQAMDVQ LHSPALQFPD VDFLKEGEDD PTVCKEIRHN STGCLKMKGQ
310 320 330 340 350
CEKCQEILSV DCSTNNPAQA NLRQELNDSL QVAERLTQQY NELLHSLQSK
360 370 380 390 400
MLNTSSLLEQ LNDQFTWVSQ LANLTQGDDQ YLRVSTVTTH SSDSEVPSRV
410 420 430 440
TEVVVKLFDS DPITVVLPEE VSKDNPKFMD TVAEKALQEY RRKSRME
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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 29, 2014
This is version 115 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