CLUS_COTJA
ID CLUS_COTJA Reviewed; 451 AA.
AC P14018;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 80.
DE RecName: Full=Clusterin;
DE AltName: Full=51.5 kDa protein;
DE Contains:
DE RecName: Full=Clusterin beta chain;
DE Contains:
DE RecName: Full=Clusterin alpha chain;
DE Flags: Precursor;
GN Name=CLU; Synonyms=T64;
OS Coturnix japonica (Japanese quail) (Coturnix coturnix japonica).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Perdicinae; Coturnix.
OX NCBI_TaxID=93934;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Neuroretina;
RX PubMed=2541393;
RA Michel D., Gillet G., Volovitch M., Pessac B., Calothy G., Brun G.;
RT "Expression of a novel gene encoding a 51.5 kD precursor protein is induced
RT by different retroviral oncogenes in quail neuroretinal cells.";
RL Oncogene Res. 4:127-136(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7744033; DOI=10.1111/j.1432-1033.1995.0215l.x;
RA Michel D., Chatelain G., Herault Y., Brun G.;
RT "The expression of the avian clusterin gene can be driven by two
RT alternative promoters with distinct regulatory elements.";
RL Eur. J. Biochem. 229:215-223(1995).
CC -!- FUNCTION: Functions as extracellular chaperone that prevents
CC aggregation of nonnative proteins. Prevents stress-induced aggregation
CC of blood plasma proteins. Does not require ATP. Maintains partially
CC unfolded proteins in a state appropriate for subsequent refolding by
CC other chaperones, such as HSPA8/HSC70. Does not refold proteins by
CC itself. Binding to cell surface receptors triggers internalization of
CC the chaperone-client complex and subsequent lysosomal or proteasomal
CC degradation. When secreted, protects cells against apoptosis and
CC against cytolysis by complement. Intracellular forms interact with
CC ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase
CC complexes and promote the ubiquitination and subsequent proteasomal
CC degradation of target proteins. Modulates NF-kappa-B transcriptional
CC activity. Promotes apoptosis when in the nucleus. Inhibits apoptosis
CC when associated with the mitochondrial membrane by interference with
CC BAX-dependent release of cytochrome c into the cytoplasm. Plays a role
CC in the regulation of cell proliferation (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Antiparallel disulfide-linked heterodimer of an alpha chain
CC and a beta chain. Self-associates and forms higher oligomers. Interacts
CC with a broad range of misfolded proteins (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted. Cytoplasmic vesicle, secretory vesicle,
CC chromaffin granule {ECO:0000250}. Nucleus {ECO:0000250}. Cytoplasm
CC {ECO:0000250}. Mitochondrion membrane {ECO:0000250}; Peripheral
CC membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}.
CC Cytoplasm, cytosol {ECO:0000250}. Endoplasmic reticulum {ECO:0000250}.
CC Note=Present in chromaffin granules. Can retrotranslocate from the
CC secretory compartments to the cytosol upon cellular stress. Detected in
CC perinuclear foci that may be aggresomes containing misfolded,
CC ubiquitinated proteins. Detected at the mitochondrion membrane upon
CC induction of apoptosis (By similarity). {ECO:0000250}.
CC -!- INDUCTION: By different retroviral oncogenes.
CC -!- PTM: Proteolytically cleaved on its way through the secretory system,
CC probably within the Golgi lumen. {ECO:0000250}.
CC -!- PTM: Polyubiquitinated, leading to proteasomal degradation.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the clusterin family. {ECO:0000305}.
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DR EMBL; X15825; CAA33823.1; -; mRNA.
DR EMBL; X80760; CAA56733.1; -; Genomic_DNA.
DR PIR; S07714; S07714.
DR AlphaFoldDB; P14018; -.
DR SMR; P14018; -.
DR Proteomes; UP000694412; Unplaced.
DR GO; GO:0042583; C:chromaffin granule; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISS:UniProtKB.
DR InterPro; IPR016016; Clusterin.
DR InterPro; IPR000753; Clusterin-like.
DR InterPro; IPR016015; Clusterin_C.
DR InterPro; IPR033986; Clusterin_CS.
DR InterPro; IPR016014; Clusterin_N.
DR PANTHER; PTHR10970; PTHR10970; 1.
DR PANTHER; PTHR10970:SF1; PTHR10970:SF1; 1.
DR Pfam; PF01093; Clusterin; 1.
DR PIRSF; PIRSF002368; Clusterin; 1.
DR SMART; SM00035; CLa; 1.
DR SMART; SM00030; CLb; 1.
DR PROSITE; PS00492; CLUSTERIN_1; 1.
DR PROSITE; PS00493; CLUSTERIN_2; 1.
PE 2: Evidence at transcript level;
KW Chaperone; Cytoplasm; Cytoplasmic vesicle; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Membrane; Mitochondrion; Nucleus;
KW Reference proteome; Secreted; Signal; Ubl conjugation.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..451
FT /note="Clusterin"
FT /id="PRO_0000005549"
FT CHAIN 19..230
FT /note="Clusterin beta chain"
FT /evidence="ECO:0000255"
FT /id="PRO_0000005550"
FT CHAIN 231..451
FT /note="Clusterin alpha chain"
FT /evidence="ECO:0000255"
FT /id="PRO_0000005551"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 141
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 278
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 355
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 375
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 447
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 98..314
FT /note="Interchain (between beta and alpha chains)"
FT /evidence="ECO:0000250"
FT DISULFID 109..306
FT /note="Interchain (between beta and alpha chains)"
FT /evidence="ECO:0000250"
FT DISULFID 112..303
FT /note="Interchain (between beta and alpha chains)"
FT /evidence="ECO:0000250"
FT DISULFID 117..296
FT /note="Interchain (between beta and alpha chains)"
FT /evidence="ECO:0000250"
FT DISULFID 125..286
FT /note="Interchain (between beta and alpha chains)"
FT /evidence="ECO:0000250"
FT CONFLICT 437
FT /note="A -> P (in Ref. 1; CAA33823)"
FT /evidence="ECO:0000305"
FT CONFLICT 445..451
FT /note="KQNNTIE -> SRTTP (in Ref. 1; CAA33823)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 451 AA; 51801 MW; 8CF811225C5B22F3 CRC64;
MELPLLALLS LGLVCQGGQG LVPPNELKQL SAAGSKYIDA EVENAINGVK QMKTLMDKTS
KEHQAMLHTL EETKKKKEEA VKLALEKEKQ LAEKQEVCNE TMLSLWEECK PCLKHTCMRV
YSKMCHSGSG LVGRQLEEFL NRSSPFSIWV NGERIDDLLD REQRQERRFE DLEERFGLME
DGVEDIFQDS TQLYGPAFPF FRTPPFGGFR EAFVPPVQRV HLVPRRRLSR ELHPFFQHPM
HGFHRLFQPL FEMTQHMLDG GHGAWEHPLG GFATESRNFS TDRMVCREIR RNSAGCLRMR
DECEKCREIL AVDCSQTDPV QSQLREQFED ALRLAERFTR RYDDLLSAFQ AEMLNTSSLL
DQLNRQFGWV SRLGNLTQGN DGFLQVTTVF SKTPNLEDPS APADTQVTVQ LFDSEPLSLT
VPGDISWDDP RFMEIVAEQA LQHYKQNNTI E
