P25473 (CLUS_CANFA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Clusterin

Alternative name(s):
Glycoprotein 80
Short name=Gp80

Cleaved into the following 2 chains:

1. Clusterin beta chain
2. Clusterin alpha chain

Gene names

Name:

CLU

Organism

Canis familiaris (Dog) (Canis lupus familiaris) [Reference proteome]

Taxonomic identifier

9615 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis › Canis lupus

Protein attributes

Sequence length	445 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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.
Subcellular location	Secreted. Cytoplasmic vesicle › secretory vesicle › chromaffin granule. Nucleus By similarity. Cytoplasm By similarity. Mitochondrion membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cytoplasm › cytosol By similarity. Microsome By similarity. Endoplasmic reticulum By similarity. Note: Present in chromaffin granules. 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.
Post-translational modification	Heavily N-glycosylated. About 30% of the protein mass is comprised of complex N-linked carbohydrate 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.
Sequence similarities	Belongs to the clusterin family.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoplasmic vesicle Endoplasmic reticulum Membrane Microsome Mitochondrion Nucleus Secreted
Domain	Signal
Molecular function	Chaperone
PTM	Disulfide bond Glycoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	chaperone-mediated protein folding Inferred from sequence or structural similarity. Source: UniProtKB intrinsic apoptotic signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of protein homooligomerization Inferred from sequence or structural similarity. Source: UniProtKB 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 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
Cellular_component	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 mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB spherical high-density lipoprotein particle Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	misfolded 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 445	423	Clusterin		PRO_0000005523
	Chain	23 – 226	204	Clusterin beta chain		PRO_0000005524
	Chain	227 – 445	219	Clusterin alpha chain		PRO_0000005525
Regions
	Motif	78 – 81	4	Nuclear localization signal By similarity
	Motif	439 – 443	5	Nuclear localization signal By similarity
Amino acid modifications
	Glycosylation	86	1	N-linked (GlcNAc...) Potential
	Glycosylation	103	1	N-linked (GlcNAc...) Potential
	Glycosylation	145	1	N-linked (GlcNAc...) Potential
	Glycosylation	277	1	N-linked (GlcNAc...) Potential
	Glycosylation	287	1	N-linked (GlcNAc...) Potential
	Glycosylation	350	1	N-linked (GlcNAc...) Potential
	Glycosylation	370	1	N-linked (GlcNAc...) Potential
	Disulfide bond	102 ↔ 309		Interchain (between beta and alpha chains) By similarity
	Disulfide bond	113 ↔ 301		Interchain (between beta and alpha chains) By similarity
	Disulfide bond	116 ↔ 298		Interchain (between beta and alpha chains) By similarity
	Disulfide bond	121 ↔ 291		Interchain (between beta and alpha chains) By similarity
	Disulfide bond	129 ↔ 281		Interchain (between beta and alpha chains) By similarity

Sequences

	Sequence		Length	Mass (Da)
	P25473 [UniParc]. Last modified May 1, 1992. Version 1. Checksum: 023A37266ABEF374	FASTA	445	51,790
	10 20 30 40 50 60 MMKTLLLLVG LLLTWDNGRV LGDQAVSDTE LQEMSTEGSK YINKEIKNAL KGVKQIKTLI 70 80 90 100 110 120 EQTNEERKSL LSNLEEAKKK KEDALNDTKD SETKLKASQG VCNDTMMALW EECKPCLKQT 130 140 150 160 170 180 CMKFYARVCR SGSGLVGHQL EEFLNQSSPF YFWMNGDRID SLLENDRQQT HALDVMQDSF 190 200 210 220 230 240 NRASSIMDEL FQDRFFTREP QDTYHYSPFS LFQRRPFFNP KFRIARNIIP FPRFQPLNFH 250 260 270 280 290 300 DMFQPFFDMI HQAQQAMDVN LHRIPYHFPI EFPEEDNRTV CKEIRHNSTG CLKMKDQCEK 310 320 330 340 350 360 CQEILSVDCS SNNPAQVQLR QELSNSLQIA EKFTKLYDEL LQSYQEKMFN TSSLLKQLNE 370 380 390 400 410 420 QFSWVSQLAN LTQSEDPFYL QVTTVGSQTS DSNVPVGFTK VVVKLFDSDP ITVMIPEAVS 430 440 RNNPKFMETV AEKALQEYRQ KHREE

References

[1]

"Molecular cloning of gp 80, a glycoprotein complex secreted by kidney cells in vitro and in vivo. A link to the reproductive system and to the complement cascade." Hartmann K., Rauch J., Urban J., Parczyk K., Diel P., Pilarsky C., Appel D., Haase W., Mann K., Weller A., Koch-Brandt C. J. Biol. Chem. 266:9924-9931(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Cocker spaniel. Tissue: Kidney.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M55251 mRNA. Translation: AAA30846.1.
PIR	A40018.
RefSeq	NP_001003370.1. NM_001003370.1.
UniGene	Cfa.1254.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	9615.ENSCAFP00000012350.
Proteomic databases
PaxDb	P25473.
PRIDE	P25473.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSCAFT00000039007; ENSCAFP00000034804; ENSCAFG00000008404.
GeneID	442971.
KEGG	cfa:442971.
Organism-specific databases
CTD	1191.
Phylogenomic databases
eggNOG	NOG26650.
GeneTree	ENSGT00530000063668.
HOGENOM	HOG000111799.
HOVERGEN	HBG006908.
Family and domain databases
InterPro	IPR016016. Clusterin. IPR000753. Clusterin-like. IPR016015. Clusterin_C. IPR016014. Clusterin_N. [Graphical view]
PANTHER	PTHR10970:SF1. PTHR10970:SF1. 1 hit.
Pfam	PF01093. Clusterin. 1 hit. [Graphical view]
PIRSF	PIRSF002368. Clusterin. 1 hit.
SMART	SM00035. CLa. 1 hit. SM00030. CLb. 1 hit. [Graphical view]
PROSITE	PS00492. CLUSTERIN_1. 1 hit. PS00493. CLUSTERIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	20831642.

Entry information

Entry name

CLUS_CANFA

Accession

Primary (citable) accession number: P25473

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	May 1, 1992
Last modified:	April 3, 2013
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program