P05371 (CLUS_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

1. Clusterin beta chain
2. Clusterin alpha chain

Gene names

Name:

Clu

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	447 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein 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. Ref.4
Subcellular location	Secreted. 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. Cytoplasmic vesicle › secretory vesicle › 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 By similarity. Ref.1 Ref.4
Tissue specificity	Detected in Sertoli cells (at protein level). Detected in cultured Sertoli cells, testis, epididymis, liver and brain. Ref.1
Developmental stage	Expressed by cells undergoing programmed death as a result of the hormonal stimuli or a traumatic insult.
Post-translational modification	Extensively glycosylated with sulfated N-linked carbohydrates. Ref.1 Proteolytically cleaved on its way through the secretory system, probably within the Golgi lumen By similarity. Ref.1 Ref.4 Polyubiquitinated, leading to proteasomal degradation By similarity.
Sequence similarities	Belongs to the clusterin family.

Ontologies

Keywords
Biological process	Differentiation Spermatogenesis
Cellular component	Cytoplasm Cytoplasmic vesicle Endoplasmic reticulum Membrane Microsome Mitochondrion Nucleus Secreted
Domain	Signal
Molecular function	Chaperone Developmental protein
PTM	Disulfide bond Glycoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to growth factor stimulus Inferred from expression pattern PubMed 16038898. Source: RGD chaperone-mediated protein folding Inferred from sequence or structural similarity. Source: UniProtKB endocrine pancreas development Inferred from mutant phenotype PubMed 16411126. Source: RGD 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 neuron projection morphogenesis Inferred from mutant phenotype PubMed 16038898. Source: RGD 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 cell differentiation Inferred from mutant phenotype PubMed 16411126. Source: RGD positive regulation of cell proliferation Inferred from mutant phenotype PubMed 15591223. Source: RGD 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 response to oxidative stress Inferred from expression pattern PubMed 14512294. Source: RGD response to wounding Inferred from expression pattern PubMed 12457227. Source: RGD spermatogenesis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	aggresome Inferred from direct assay PubMed 12799419. Source: RGD 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 growth cone Inferred from direct assay PubMed 16038898. Source: RGD mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from direct assay PubMed 16038898. Source: RGD 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 – 21	21	Ref.1 Ref.4
	Chain	22 – 447	426	Clusterin		PRO_0000005544
	Chain	22 – 226	205	Clusterin beta chain		PRO_0000005545
	Chain	227 – 447	221	Clusterin alpha chain		PRO_0000005546
Regions
	Motif	77 – 80	4	Nuclear localization signal By similarity
	Motif	441 – 445	5	Nuclear localization signal By similarity
Amino acid modifications
	Glycosylation	102	1	N-linked (GlcNAc...) Probable
	Glycosylation	144	1	N-linked (GlcNAc...) Probable
	Glycosylation	290	1	N-linked (GlcNAc...) Probable
	Glycosylation	327	1	N-linked (GlcNAc...) Probable
	Glycosylation	353	1	N-linked (GlcNAc...) Probable
	Glycosylation	373	1	N-linked (GlcNAc...) Probable
	Disulfide bond	101 ↔ 312		Interchain (between beta and alpha chains) By similarity
	Disulfide bond	112 ↔ 304		Interchain (between beta and alpha chains) By similarity
	Disulfide bond	115 ↔ 301		Interchain (between beta and alpha chains) By similarity
	Disulfide bond	120 ↔ 294		Interchain (between beta and alpha chains) By similarity
	Disulfide bond	128 ↔ 284		Interchain (between beta and alpha chains) By similarity
Experimental info
	Sequence conflict	187	1	D → H in AAA41273. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P05371 [UniParc]. Last modified February 1, 1994. Version 2. Checksum: 9E2FA33E5E0C146E	FASTA	447	51,375
	10 20 30 40 50 60 MKILLLCVAL LLTWDNGMVL GEQEFSDNEL QELSTQGSRY VNKEIQNAVQ GVKHIKTLIE 70 80 90 100 110 120 KTNAERKSLL NSLEEAKKKK EGALDDTRDS EMKLKAFPEV CNETMMALWE ECKPCLKHTC 130 140 150 160 170 180 MKFYARVCRS GSGLVGRQLE EFLNQSSPFY FWMNGDRIDS LLESDRQQSQ VLDAMQDSFT 190 200 210 220 230 240 RASGIIDTLF QDRFFTHEPQ DIHHFSPMGF PHKRPHFLYP KSRLVRSLMP LSHYGPLSFH 250 260 270 280 290 300 NMFQPFFDMI HQAQQAMDVQ LHSPALQFPD VDFLKEGEDD PTVCKEIRHN STGCLKMKGQ 310 320 330 340 350 360 CEKCQEILSV DCSTNNPAQA NLRQELNDSL QVAERLTQQY NELLHSLQSK MLNTSSLLEQ 370 380 390 400 410 420 LNDQFTWVSQ LANLTQGDDQ YLRVSTVTTH SSDSEVPSRV TEVVVKLFDS DPITVVLPEE 430 440 VSKDNPKFMD TVAEKALQEY RRKSRME

References

[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M16975 mRNA. Translation: AAA41273.1. X13231 mRNA. Translation: CAA31618.1. M64723 mRNA. Translation: AAA42298.1. M64733 Genomic DNA. Translation: AAA42299.1.
IPI	IPI00198667.
PIR	A27205. A45890.
RefSeq	NP_444180.2. NM_053021.2.
UniGene	Rn.1780.
3D structure databases
DisProt	DP00014.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-4586114.
Proteomic databases
PaxDb	P05371.
PRIDE	P05371.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	24854.
KEGG	rno:24854.
UCSC	RGD:3907. rat.
Organism-specific databases
CTD	1191.
RGD	3907. Clu.
Phylogenomic databases
eggNOG	NOG26650.
HOGENOM	HOG000111799.
HOVERGEN	HBG006908.
InParanoid	P05371.
OrthoDB	EOG447FTH.
Gene expression databases
ArrayExpress	P05371.
Genevestigator	P05371.
GermOnline	ENSRNOG00000016460. Rattus norvegicus.
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	604646.

Entry information

Entry name

CLUS_RAT

Accession

Primary (citable) accession number: P05371

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	February 1, 1994
Last modified:	April 3, 2013
This is version 105 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program