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Protein

Clusterin

Gene

CLU

Organism
Bos taurus (Bovine)
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-BTA-114608. Platelet degranulation.

Names & Taxonomyi

Protein namesi
Recommended name:
Clusterin
Alternative name(s):
Glycoprotein III
Short name:
GpIII
Cleaved into the following 2 chains:
Gene namesi
Name:CLU
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 8

Subcellular locationi

GO - Cellular componenti

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 – 19191 PublicationAdd
BLAST
Chaini20 – 439420ClusterinPRO_0000005520Add
BLAST
Chaini20 – 221202Clusterin beta chainPRO_0000005521Add
BLAST
Chaini222 – 439218Clusterin alpha chainPRO_0000005522Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi80 – 801N-linked (GlcNAc...)Sequence analysis
Disulfide bondi96 ↔ 305Interchain (between beta and alpha chains)By similarity
Glycosylationi97 – 971N-linked (GlcNAc...)Sequence analysis
Disulfide bondi107 ↔ 297Interchain (between beta and alpha chains)By similarity
Disulfide bondi110 ↔ 294Interchain (between beta and alpha chains)By similarity
Disulfide bondi115 ↔ 287Interchain (between beta and alpha chains)By similarity
Disulfide bondi123 ↔ 277Interchain (between beta and alpha chains)By similarity
Modified residuei127 – 1271PhosphoserineBy similarity
Glycosylationi139 – 1391N-linked (GlcNAc...)Sequence analysis
Glycosylationi283 – 2831N-linked (GlcNAc...)Sequence analysis
Glycosylationi309 – 3091N-linked (GlcNAc...)Sequence analysis
Glycosylationi320 – 3201N-linked (GlcNAc...)Sequence analysis
Glycosylationi346 – 3461N-linked (GlcNAc...)Sequence analysis
Glycosylationi366 – 3661N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

Heavily N-glycosylated. About 30% of the protein mass is comprised of complex N-linked carbohydrate (By similarity).By similarity
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

PaxDbiP17697.
PRIDEiP17697.

Expressioni

Tissue specificityi

Expressed abundantly in liver, testis, and brain.

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi158151. 1 interaction.
STRINGi9913.ENSBTAP00000007324.

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi72 – 754Nuclear localization signalBy similarity
Motifi433 – 4375Nuclear localization signalBy similarity

Sequence similaritiesi

Belongs to the clusterin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IHRB. Eukaryota.
ENOG410YYKB. LUCA.
GeneTreeiENSGT00530000063668.
HOGENOMiHOG000111799.
HOVERGENiHBG006908.
InParanoidiP17697.
KOiK17252.
OMAiMKFYARV.
OrthoDBiEOG7K6PV4.
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.

P17697-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKTLLLLMGL LLSWESGWAI SDKELQEMST EGSKYVNKEI KNALKEVKQI
60 70 80 90 100
KTQIEQTNEE RKLLLSSLEE AKKKKEDALN DTRDSENKLK ASQGVCNETM
110 120 130 140 150
TALWEECKPC LKQTCMKFYA RVCRSGSGLV GHQLEEFLNQ SSPFYFWING
160 170 180 190 200
DRIDSLMEND REQSHVMDVM EDSFTRASSI MDELFQDRFF LRRPQDTQYY
210 220 230 240 250
SPFSSFPRGS LFFNPKSRFA RNVMPFPLLE PFNFHDVFQP FYDMIHQAQQ
260 270 280 290 300
AMDAHLQRTP YHFPTMEFTE NNDRTVCKEI RHNSTGCLRM KDQCEKCQEI
310 320 330 340 350
LEVDCSASNP TQTLLRQQLN ASLQLAEKFS RLYDQLLQSY QQKMLNTSAL
360 370 380 390 400
LKQLNEQFTW VSQLANLTQS DDQHYLQVFT VNSHNSDPSI PSGLTKVIVK
410 420 430
LFNSFPITVT VPQEVSSPNF MENVAEKALQ QYRRKSQEE
Length:439
Mass (Da):51,114
Last modified:August 1, 1990 - v1
Checksum:i36979481A61B02DE
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05391 mRNA. Translation: AAA30554.1.
BT030502 mRNA. Translation: ABQ12942.1.
BC118223 mRNA. Translation: AAI18224.1.
BC149632 mRNA. Translation: AAI49633.1.
PIRiA35744.
RefSeqiNP_776327.1. NM_173902.2.
XP_005209898.1. XM_005209841.1.
XP_010806015.1. XM_010807713.1.
UniGeneiBt.12504.

Genome annotation databases

EnsembliENSBTAT00000007324; ENSBTAP00000007324; ENSBTAG00000005574.
GeneIDi280750.
KEGGibta:280750.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05391 mRNA. Translation: AAA30554.1.
BT030502 mRNA. Translation: ABQ12942.1.
BC118223 mRNA. Translation: AAI18224.1.
BC149632 mRNA. Translation: AAI49633.1.
PIRiA35744.
RefSeqiNP_776327.1. NM_173902.2.
XP_005209898.1. XM_005209841.1.
XP_010806015.1. XM_010807713.1.
UniGeneiBt.12504.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi158151. 1 interaction.
STRINGi9913.ENSBTAP00000007324.

Proteomic databases

PaxDbiP17697.
PRIDEiP17697.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000007324; ENSBTAP00000007324; ENSBTAG00000005574.
GeneIDi280750.
KEGGibta:280750.

Organism-specific databases

CTDi1191.

Phylogenomic databases

eggNOGiENOG410IHRB. Eukaryota.
ENOG410YYKB. LUCA.
GeneTreeiENSGT00530000063668.
HOGENOMiHOG000111799.
HOVERGENiHBG006908.
InParanoidiP17697.
KOiK17252.
OMAiMKFYARV.
OrthoDBiEOG7K6PV4.
TreeFamiTF333030.

Enzyme and pathway databases

ReactomeiR-BTA-114608. Platelet degranulation.

Miscellaneous databases

NextBioi20804918.

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...

Publicationsi

« Hide 'large scale' publications
  1. "The primary structure of glycoprotein III from bovine adrenal medullary chromaffin granules. Sequence similarity with human serum protein-40,40 and rat Sertoli cell glycoprotein."
    Palmer D.J., Christie D.L.
    J. Biol. Chem. 265:6617-6623(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 20-32 AND 222-240.
    Tissue: Chromaffin cell.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. NIH - Mammalian Gene Collection (MGC) project
    Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Fetal pons and Hippocampus.

Entry informationi

Entry nameiCLUS_BOVIN
AccessioniPrimary (citable) accession number: P17697
Secondary accession number(s): A5D983, Q148K1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: November 11, 2015
This is version 107 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, Direct protein sequencing, Reference proteome

Documents

  1. 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.