Q06890 (CLUS_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Clusterin

Alternative name(s):
Apolipoprotein J
Short name=Apo-J
Clustrin
Sulfated glycoprotein 2
Short name=SGP-2

Cleaved into the following 2 chains:

1. Clusterin beta chain
2. Clusterin alpha chain

Gene names

Name:	Clu
Synonyms:	Apoj, Msgp-2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [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 › Mus › Mus

Protein attributes

Sequence length	448 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 By similarity. Interacts (via alpha chain) with XRCC6. Found in a complex with LTF, CLU, EPPIN and SEMG1 By similarity. Ref.7
Subcellular location	Secreted. Nucleus. Cytoplasm. Mitochondrion membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cytoplasm › cytosol. 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.7
Tissue specificity	Most abundant in stomach, liver, brain, and testis, with intermediate levels in heart, ovary and kidney.
Post-translational modification	Extensively glycosylated with sulfated N-linked carbohydrates. Proteolytically cleaved on its way through the secretory system, probably within the Golgi lumen By similarity. Polyubiquitinated, leading to proteasomal degradation By similarity.
Disruption phenotype	No visible phenotype. During myocarditis, mice show an increased tendency to cardiac tissue injury. Ref.6
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 response to virus Inferred from electronic annotation. Source: Compara
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 extracellular matrix Inferred from electronic annotation. Source: Compara 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 – 21	21	By similarity
	Chain	22 – 448	427	Clusterin		PRO_0000005535
	Chain	22 – 226	205	Clusterin beta chain By similarity		PRO_0000005536
	Chain	227 – 447	221	Clusterin alpha chain By similarity		PRO_0000005537
Regions
	Motif	77 – 80	4	Nuclear localization signal
	Motif	442 – 446	5	Nuclear localization signal
Amino acid modifications
	Glycosylation	102	1	N-linked (GlcNAc...) Probable
	Glycosylation	144	1	N-linked (GlcNAc...) Probable
	Glycosylation	290	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	327	1	N-linked (GlcNAc...) Ref.8
	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
	Mutagenesis	78 – 79	2	KK → AV: Reduced nuclear location.
	Mutagenesis	343	1	L → P: Abolishes interaction with XRCC6. Ref.7
	Mutagenesis	357 – 358	2	LL → RQ: Abolishes interaction with XRCC6.
	Mutagenesis	361	1	L → R: Abolishes interaction with XRCC6. Ref.7
	Mutagenesis	371	1	L → R: Strongly reduced interaction with XRCC6. Ref.7
	Mutagenesis	442 – 443	2	RR → VV: Strongly reduced nuclear location.
	Sequence conflict	10	1	L → M in AAB30623. Ref.3
	Sequence conflict	335 – 336	2	RL → TV in AAA37284. Ref.4
	Sequence conflict	350	1	K → N in AAA37284. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q06890 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: A860600A6F8D47F6	FASTA	448	51,656
	10 20 30 40 50 60 MKILLLCVAL LLIWDNGMVL GEQEVSDNEL QELSTQGSRY INKEIQNAVQ GVKHIKTLIE 70 80 90 100 110 120 KTNAERKSLL NSLEEAKKKK EDALEDTRDS EMKLKAFPEV CNETMMALWE ECKPCLKHTC 130 140 150 160 170 180 MKFYARVCRS GSGLVGQQLE EFLNQSSPFY FWMNGDRIDS LLESDRQQSQ VLDAMQDSFA 190 200 210 220 230 240 RASGIIDTLF QDRFFARELH DPHYFSPIGF PHKRPHFLYP KSRLVRSLMS PSHYGPPSFH 250 260 270 280 290 300 NMFQPFFEMI HQAQQAMDVQ LHSPAFQFPD VDFLREGEDD RTVCKEIRRN STGCLKMKGQ 310 320 330 340 350 360 CEKCQEILSV DCSTNNPAQA NLRQELNDSL QVAERLTEQY KELLQSFQSK MLNTSSLLEQ 370 380 390 400 410 420 LNDQFNWVSQ LANLTQGEDK YYLRVSTVTT HSSDSEVPSR VTEVVVKLFD SDPITVVLPE 430 440 EVSKDNPKFM DTVAEKALQE YRRKSRAE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and sequencing of sulfated glycoprotein-2 cDNA from testis of mouse: implications of two different mRNAs of SGP-2." Lee K.-H., Ji Y.-M., Lim H.M., Lee S.-C., You K.-H. Biochem. Biophys. Res. Commun. 194:1175-1180(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[2]	"Murine clusterin: molecular cloning and mRNA localization of a gene associated with epithelial differentiation processes during embryogenesis." French L.E., Chonn A., Ducrest D., Baumann B., Belin D., Wohlwend A., Kiss J.Z., Sappino A.P., Tschopp J., Schifferli J.A. J. Cell Biol. 122:1119-1130(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c. Tissue: Heart.
[3]	"Mouse apolipoprotein J: characterization of a gene implicated in atherosclerosis." Jordan-Starck T.C., Lund S.D., Witte D.P., Aronow B.J., Ley C.A., Stuart W.D., Swertfeger D.K., Clayton L.R., Sells S.F., Paigen B. J. Lipid Res. 35:194-210(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6 X CBA. Tissue: Liver.
[4]	"Secretion of sulfated glycoprotein (clustrin) accompanies cytodifferentiation and structural remodeling of mouse BC3H1 myogenic cells." Hodgdon B.A., Min B.H., Yan H., Farris J.A., Foster D.N., Strauch A.R. Submitted (NOV-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Eye.
[6]	"Apolipoprotein J/clusterin limits the severity of murine autoimmune myocarditis." McLaughlin L., Zhu G., Mistry M., Ley-Ebert C., Stuart W.D., Florio C.J., Groen P.A., Witt S.A., Kimball T.R., Witte D.P., Harmony J.A., Aronow B.J. J. Clin. Invest. 106:1105-1113(2000) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[7]	"Synthesis and functional analyses of nuclear clusterin, a cell death protein." Leskov K.S., Klokov D.Y., Li J., Kinsella T.J., Boothman D.A. J. Biol. Chem. 278:11590-11600(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH XRCC6, SUBCELLULAR LOCATION, MUTAGENESIS OF 78-LYS-LYS-79; LEU-343; 357-LEU-LEU-358; LEU-361; LEU-371 AND 442-ARG-ARG-443.
[8]	"Proteome-wide characterization of N-glycosylation events by diagonal chromatography." Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K. J. Proteome Res. 5:2438-2447(2006) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-327, MASS SPECTROMETRY. Strain: C57BL/6. Tissue: Plasma.
[9]	"Enhanced analysis of the mouse plasma proteome using cysteine-containing tryptic glycopeptides." Bernhard O.K., Kapp E.A., Simpson R.J. J. Proteome Res. 6:987-995(2007) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-290, MASS SPECTROMETRY. Strain: C57BL/6. Tissue: Plasma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D14077 mRNA. Translation: BAA03162.1. L08235 mRNA. Translation: AAA37422.1. S70244 mRNA. Translation: AAB30623.1. L05670 mRNA. Translation: AAA37284.1. BC075668 mRNA. Translation: AAH75668.1.
IPI	IPI00320420.
PIR	A40714. I56335.
RefSeq	NP_038520.2. NM_013492.2.
UniGene	Mm.200608.
3D structure databases
ProteinModelPortal	Q06890.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q06890. 2 interactions.
MINT	MINT-1176977.
PTM databases
PhosphoSite	Q06890.
Proteomic databases
PaxDb	Q06890.
PRIDE	Q06890.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000022616; ENSMUSP00000022616; ENSMUSG00000022037.
GeneID	12759.
KEGG	mmu:12759.
Organism-specific databases
CTD	1191.
MGI	MGI:88423. Clu.
Phylogenomic databases
eggNOG	NOG26650.
HOGENOM	HOG000111799.
HOVERGEN	HBG006908.
InParanoid	Q06890.
OMA	SSPFYFW.
Gene expression databases
ArrayExpress	Q06890.
Bgee	Q06890.
CleanEx	MM_CLU.
Genevestigator	Q06890.
GermOnline	ENSMUSG00000022037. Mus musculus.
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
ChiTaRS	CLU. mouse.
NextBio	282108.
SOURCE	Search...

Entry information

Entry name

CLUS_MOUSE

Accession

Primary (citable) accession number: Q06890

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	April 3, 2013
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program