UniProtKB - P25473 (CLUS_CANLF)
Clusterin
CLU
Functioni
GO - Molecular functioni
- amyloid-beta binding Source: Ensembl
- chaperone binding Source: ParkinsonsUK-UCL
- low-density lipoprotein particle receptor binding Source: Ensembl
- misfolded protein binding Source: UniProtKB
- protein-containing complex binding Source: Ensembl
- tau protein binding Source: Ensembl
- ubiquitin protein ligase binding Source: UniProtKB
- unfolded protein binding Source: UniProtKB
GO - Biological processi
- cell morphogenesis Source: Ensembl
- central nervous system myelin maintenance Source: Ensembl
- chaperone-mediated protein complex assembly Source: Ensembl
- chaperone-mediated protein folding Source: UniProtKB
- immune complex clearance Source: UniProtKB
- intrinsic apoptotic signaling pathway Source: UniProtKB
- microglial cell activation Source: Ensembl
- microglial cell proliferation Source: Ensembl
- negative regulation of amyloid-beta formation Source: Ensembl
- negative regulation of amyloid fibril formation Source: UniProtKB
- negative regulation of cellular response to thapsigargin Source: Ensembl
- negative regulation of cellular response to tunicamycin Source: Ensembl
- negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage Source: BHF-UCL
- negative regulation of protein-containing complex assembly Source: BHF-UCL
- negative regulation of response to endoplasmic reticulum stress Source: Ensembl
- positive regulation of amyloid-beta formation Source: Ensembl
- positive regulation of apoptotic process Source: UniProtKB
- positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
- positive regulation of neurofibrillary tangle assembly Source: Ensembl
- positive regulation of neuron death Source: Ensembl
- positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
- positive regulation of nitric oxide biosynthetic process Source: Ensembl
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
- positive regulation of protein-containing complex assembly Source: Ensembl
- positive regulation of receptor-mediated endocytosis Source: UniProtKB
- positive regulation of tau-protein kinase activity Source: Ensembl
- positive regulation of tumor necrosis factor production Source: Ensembl
- positive regulation of ubiquitin-dependent protein catabolic process Source: UniProtKB
- protein import Source: Ensembl
- protein stabilization Source: UniProtKB
- regulation of amyloid-beta clearance Source: Ensembl
- regulation of apoptotic process Source: GO_Central
- regulation of cell population proliferation Source: UniProtKB
- regulation of neuronal signal transduction Source: Ensembl
- response to misfolded protein Source: UniProtKB
- response to virus Source: Ensembl
Keywordsi
Molecular function | Chaperone |
Enzyme and pathway databases
Reactomei | R-CFA-114608, Platelet degranulation R-CFA-166665, Terminal pathway of complement R-CFA-6803157, Antimicrobial peptides R-CFA-977606, Regulation of Complement cascade |
Names & Taxonomyi
Protein namesi | Recommended name: ClusterinAlternative name(s): Glycoprotein 801 Publication Short name: Gp801 Publication Cleaved into the following 2 chains: |
Gene namesi | Name:CLU |
Organismi | Canis lupus familiaris (Dog) (Canis familiaris) |
Taxonomic identifieri | 9615 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis › |
Proteomesi |
|
Organism-specific databases
VGNCi | VGNC:39369, CLU |
Subcellular locationi
Cytosol
- cytosol By similarity
Endoplasmic reticulum
- Microsome By similarity
- Endoplasmic reticulum By similarity
Mitochondrion
- Mitochondrion membrane By similarity; Peripheral membrane protein By similarity; Cytoplasmic side By similarity
- Mitochondrion By similarity
- Mitochondrion membrane By similarity
Extracellular region or secreted
- Secreted By similarity
Nucleus
- Nucleus By similarity
Other locations
- Cytoplasm By similarity
- perinuclear region By similarity
- chromaffin 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. Under ER stress, a immaturely glycosylated pre-secreted form retrotranslocates from the endoplasmic reticulum (ER)-Golgi network to the cytoplasm to localize in the mitochondria through HSPA5 interaction. ER stress reduces secretion. Under the stress, minor amounts of non-secreted forms accumulate in cytoplasm.By similarity
Cytoskeleton
- cytoskeleton Source: Ensembl
Cytosol
- cytosol Source: UniProtKB
Endoplasmic reticulum
- endoplasmic reticulum lumen Source: ParkinsonsUK-UCL
- perinuclear endoplasmic reticulum lumen Source: UniProtKB
Extracellular region or secreted
- extracellular space Source: UniProtKB
- spherical high-density lipoprotein particle Source: UniProtKB
Golgi apparatus
- Golgi apparatus Source: ParkinsonsUK-UCL
Mitochondrion
- mitochondrial inner membrane Source: UniProtKB
- mitochondrion Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Other locations
- apical dendrite Source: Ensembl
- cell periphery Source: Ensembl
- cell surface Source: Ensembl
- chromaffin granule Source: UniProtKB-SubCell
- neurofibrillary tangle Source: Ensembl
- perinuclear region of cytoplasm Source: UniProtKB
- synapse Source: Ensembl
Keywords - Cellular componenti
Cytoplasm, Cytoplasmic vesicle, Endoplasmic reticulum, Membrane, Microsome, Mitochondrion, Nucleus, SecretedPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 22 | Sequence analysisAdd BLAST | 22 | |
ChainiPRO_0000005523 | 23 – 445 | ClusterinAdd BLAST | 423 | |
ChainiPRO_0000005524 | 23 – 226 | Clusterin beta chainAdd BLAST | 204 | |
ChainiPRO_0000005525 | 227 – 445 | Clusterin alpha chainAdd BLAST | 219 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 86 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 102 ↔ 309 | Interchain (between beta and alpha chains)By similarity | ||
Glycosylationi | 103 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 113 ↔ 301 | Interchain (between beta and alpha chains)By similarity | ||
Disulfide bondi | 116 ↔ 298 | Interchain (between beta and alpha chains)By similarity | ||
Disulfide bondi | 121 ↔ 291 | Interchain (between beta and alpha chains)By similarity | ||
Disulfide bondi | 129 ↔ 281 | Interchain (between beta and alpha chains)By similarity | ||
Modified residuei | 133 | PhosphoserineBy similarity | 1 | |
Glycosylationi | 145 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 277 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 287 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 350 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 370 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 392 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | P25473 |
PRIDEi | P25473 |
Expressioni
Gene expression databases
Bgeei | ENSCAFG00000008404, Expressed in thyroid gland and 49 other tissues |
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 (via alpha chain) with XRCC6.
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.
Found in a complex with LTF, CLU, EPPIN and SEMG1.
Interacts (immaturely glycosylated pre-secreted form) with HSPA5; this interaction promotes CLU stability and facilitates stress-induced CLU retrotranslocation from the secretory pathway to the mitochondria, thereby reducing stress-induced apoptosis by stabilizing mitochondrial membrane integrity.
Interacts with BCL2L1; this interaction releases and activates BAX and promotes cell death.
Interacts with TGFBR2 and ACVR1 (By similarity).
Interacts (secreted form) with STMN3; this interaction may act as an important modulator during neuronal differentiation (By similarity).
By similarityGO - Molecular functioni
- chaperone binding Source: ParkinsonsUK-UCL
- low-density lipoprotein particle receptor binding Source: Ensembl
- misfolded protein binding Source: UniProtKB
- tau protein binding Source: Ensembl
- ubiquitin protein ligase binding Source: UniProtKB
- unfolded protein binding Source: UniProtKB
Protein-protein interaction databases
STRINGi | 9612.ENSCAFP00000012350 |
Family & Domainsi
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 78 – 81 | Nuclear localization signalBy similarity | 4 | |
Motifi | 439 – 443 | Nuclear localization signalBy similarity | 5 |
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502RBQP, Eukaryota |
GeneTreei | ENSGT00530000063668 |
HOGENOMi | CLU_042162_2_0_1 |
InParanoidi | P25473 |
OrthoDBi | 973835at2759 |
Family and domain databases
InterProi | View protein in InterPro IPR016016, Clusterin IPR000753, Clusterin-like IPR016015, Clusterin_C IPR033986, Clusterin_CS IPR016014, Clusterin_N |
PANTHERi | PTHR10970, PTHR10970, 1 hit PTHR10970:SF1, PTHR10970:SF1, 1 hit |
Pfami | View protein in Pfam PF01093, Clusterin, 1 hit |
PIRSFi | PIRSF002368, Clusterin, 1 hit |
SMARTi | View protein in SMART SM00035, CLa, 1 hit SM00030, CLb, 1 hit |
PROSITEi | View protein in PROSITE PS00492, CLUSTERIN_1, 1 hit PS00493, CLUSTERIN_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MMKTLLLLVG LLLTWDNGRV LGDQAVSDTE LQEMSTEGSK YINKEIKNAL
60 70 80 90 100
KGVKQIKTLI EQTNEERKSL LSNLEEAKKK KEDALNDTKD SETKLKASQG
110 120 130 140 150
VCNDTMMALW EECKPCLKQT CMKFYARVCR SGSGLVGHQL EEFLNQSSPF
160 170 180 190 200
YFWMNGDRID SLLENDRQQT HALDVMQDSF NRASSIMDEL FQDRFFTREP
210 220 230 240 250
QDTYHYSPFS LFQRRPFFNP KFRIARNIIP FPRFQPLNFH DMFQPFFDMI
260 270 280 290 300
HQAQQAMDVN LHRIPYHFPI EFPEEDNRTV CKEIRHNSTG CLKMKDQCEK
310 320 330 340 350
CQEILSVDCS SNNPAQVQLR QELSNSLQIA EKFTKLYDEL LQSYQEKMFN
360 370 380 390 400
TSSLLKQLNE QFSWVSQLAN LTQSEDPFYL QVTTVGSQTS DSNVPVGFTK
410 420 430 440
VVVKLFDSDP ITVMIPEAVS RNNPKFMETV AEKALQEYRQ KHREE
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A5S6DEE6 | A0A5S6DEE6_CANLF | Clusterin | CLU | 467 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M55251 mRNA Translation: AAA30846.1 |
PIRi | A40018 |
RefSeqi | NP_001003370.1, NM_001003370.1 |
Genome annotation databases
Ensembli | ENSCAFT00000013347; ENSCAFP00000012350; ENSCAFG00000008404 ENSCAFT00040032862; ENSCAFP00040028589; ENSCAFG00040017797 |
GeneIDi | 442971 |
KEGGi | cfa:442971 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M55251 mRNA Translation: AAA30846.1 |
PIRi | A40018 |
RefSeqi | NP_001003370.1, NM_001003370.1 |
3D structure databases
SMRi | P25473 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9612.ENSCAFP00000012350 |
Proteomic databases
PaxDbi | P25473 |
PRIDEi | P25473 |
Genome annotation databases
Ensembli | ENSCAFT00000013347; ENSCAFP00000012350; ENSCAFG00000008404 ENSCAFT00040032862; ENSCAFP00040028589; ENSCAFG00040017797 |
GeneIDi | 442971 |
KEGGi | cfa:442971 |
Organism-specific databases
CTDi | 1191 |
VGNCi | VGNC:39369, CLU |
Phylogenomic databases
eggNOGi | ENOG502RBQP, Eukaryota |
GeneTreei | ENSGT00530000063668 |
HOGENOMi | CLU_042162_2_0_1 |
InParanoidi | P25473 |
OrthoDBi | 973835at2759 |
Enzyme and pathway databases
Reactomei | R-CFA-114608, Platelet degranulation R-CFA-166665, Terminal pathway of complement R-CFA-6803157, Antimicrobial peptides R-CFA-977606, Regulation of Complement cascade |
Gene expression databases
Bgeei | ENSCAFG00000008404, Expressed in thyroid gland and 49 other tissues |
Family and domain databases
InterProi | View protein in InterPro IPR016016, Clusterin IPR000753, Clusterin-like IPR016015, Clusterin_C IPR033986, Clusterin_CS IPR016014, Clusterin_N |
PANTHERi | PTHR10970, PTHR10970, 1 hit PTHR10970:SF1, PTHR10970:SF1, 1 hit |
Pfami | View protein in Pfam PF01093, Clusterin, 1 hit |
PIRSFi | PIRSF002368, Clusterin, 1 hit |
SMARTi | View protein in SMART SM00035, CLa, 1 hit SM00030, CLb, 1 hit |
PROSITEi | View protein in PROSITE PS00492, CLUSTERIN_1, 1 hit PS00493, CLUSTERIN_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CLUS_CANLF | |
Accessioni | P25473Primary (citable) accession number: P25473 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 1, 1992 |
Last sequence update: | May 1, 1992 | |
Last modified: | December 2, 2020 | |
This is version 120 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families