Gene/Proteome Database (LMPD)

LMPD ID
LMP012442
Gene ID
24854
Species
Rattus norvegicus (Rat)
Gene Name
clusterin
Gene Symbol
Clu
Synonyms
CLI; DAG; APOJ; SGP2; SP40; SGP-2; SP-40; Trpm2; Trpmb; TRPM-2; TRPM2B; RATTRPM2B;
Alternate Names
clusterin; sulfated glycoprotein 2; dimeric acid glycoprotein; testosterone-repressed prostate message; testostrone-repressed prostate message 2; testosterone repressed prostate message 2;
Chromosome
15
Map Location
15p12
Summary
The protein encoded by this gene is a secreted chaperone that can under some stress conditions also be found in the cell cytosol. It has been suggested to be involved in several basic biological events such as cell death, tumor progression, and neurodegenerative disorders.[provided by RefSeq, May 2011]
Orthologs
View orthologs and multiple alignments for Clu

Proteins

clusterin precursor
Refseq ID NP_444180
Protein GI 46048420
UniProt ID P05371
mRNA ID NM_053021
Length 447
MKILLLCVALLLTWDNGMVLGEQEFSDNELQELSTQGSRYVNKEIQNAVQGVKHIKTLIEKTNAERKSLLNSLEEAKKKKEGALDDTRDSEMKLKAFPEVCNETMMALWEECKPCLKHTCMKFYARVCRSGSGLVGRQLEEFLNQSSPFYFWMNGDRIDSLLESDRQQSQVLDAMQDSFTRASGIIHTLFQDRFFTHEPQDIHHFSPMGFPHKRPHFLYPKSRLVRSLMPLSHYGPLSFHNMFQPFFDMIHQAQQAMDVQLHSPALQFPDVDFLKEGEDDPTVCKEIRHNSTGCLKMKGQCEKCQEILSVDCSTNNPAQANLRQELNDSLQVAERLTQQYNELLHSLQSKMLNTSSLLEQLNDQFTWVSQLANLTQGDDQYLRVSTVTTHSSDSEVPSRVTEVVVKLFDSDPITVVLPEEVSKDNPKFMDTVAEKALQEYRRKSRME
sig_peptide: 1..21 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2317 peptide sequence: MKILLLCVALLLTWDNGMVLG mat_peptide: 227..447 product: sulfated glycoprotein 2 calculated_mol_wt: 25194 peptide sequence: SLMPLSHYGPLSFHNMFQPFFDMIHQAQQAMDVQLHSPALQFPDVDFLKEGEDDPTVCKEIRHNSTGCLKMKGQCEKCQEILSVDCSTNNPAQANLRQELNDSLQVAERLTQQYNELLHSLQSKMLNTSSLLEQLNDQFTWVSQLANLTQGDDQYLRVSTVTTHSSDSEVPSRVTEVVVKLFDSDPITVVLPEEVSKDNPKFMDTVAEKALQEYRRKSRME

Gene Information

Entrez Gene ID
24854
Gene Name
clusterin
Gene Symbol
Clu
Species
Rattus norvegicus

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0016235 IDA:RGD C aggresome
GO:0097440 ISS:Alzheimers_University_of_Toronto C apical dendrite
GO:0005737 ISS:Alzheimers_University_of_Toronto C cytoplasm
GO:0031410 IEA:UniProtKB-KW C cytoplasmic vesicle
GO:0005783 IEA:UniProtKB-KW C endoplasmic reticulum
GO:0005615 ISS:UniProtKB C extracellular space
GO:0030426 IDA:RGD C growth cone
GO:0016020 IEA:UniProtKB-KW C membrane
GO:0005739 IEA:UniProtKB-KW C mitochondrion
GO:0097418 ISS:Alzheimers_University_of_Toronto C neurofibrillary tangle
GO:0043005 IDA:RGD C neuron projection
GO:0005634 IDA:RGD C nucleus
GO:0048471 IDA:RGD C perinuclear region of cytoplasm
GO:0034366 ISS:UniProtKB C spherical high-density lipoprotein particle
GO:0051787 ISS:UniProtKB F misfolded protein binding
GO:0047485 IPI:RGD F protein N-terminus binding
GO:0031625 ISS:UniProtKB F ubiquitin protein ligase binding
GO:0007568 IEP:RGD P aging
GO:0000902 ISS:Alzheimers_University_of_Toronto P cell morphogenesis
GO:0071363 IEP:RGD P cellular response to growth factor stimulus
GO:0032286 ISS:Alzheimers_University_of_Toronto P central nervous system myelin maintenance
GO:0051131 ISS:Alzheimers_University_of_Toronto P chaperone-mediated protein complex assembly
GO:0061077 ISS:UniProtKB P chaperone-mediated protein folding
GO:0031018 IMP:RGD P endocrine pancreas development
GO:0044849 IEP:RGD P estrous cycle
GO:0097193 ISS:UniProtKB P intrinsic apoptotic signaling pathway
GO:0001774 ISS:Alzheimers_University_of_Toronto P microglial cell activation
GO:0061518 ISS:Alzheimers_University_of_Toronto P microglial cell proliferation
GO:0043066 IMP:RGD P negative regulation of apoptotic process
GO:1902430 ISS:Alzheimers_University_of_Toronto P negative regulation of beta-amyloid formation
GO:1902230 ISS:BHF-UCL P negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage
GO:0032463 ISS:UniProtKB P negative regulation of protein homooligomerization
GO:0048812 IMP:RGD P neuron projection morphogenesis
GO:0051092 ISS:UniProtKB P positive regulation of NF-kappaB transcription factor activity
GO:0043065 ISS:UniProtKB P positive regulation of apoptotic process
GO:1902004 ISS:Alzheimers_University_of_Toronto P positive regulation of beta-amyloid formation
GO:0045597 IMP:RGD P positive regulation of cell differentiation
GO:0008284 IMP:RGD P positive regulation of cell proliferation
GO:2001244 ISS:UniProtKB P positive regulation of intrinsic apoptotic signaling pathway
GO:1902998 ISS:Alzheimers_University_of_Toronto P positive regulation of neurofibrillary tangle assembly
GO:1901216 ISS:Alzheimers_University_of_Toronto P positive regulation of neuron death
GO:0045429 ISS:Alzheimers_University_of_Toronto P positive regulation of nitric oxide biosynthetic process
GO:0032436 ISS:UniProtKB P positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:2000060 ISS:UniProtKB P positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:1902949 ISS:Alzheimers_University_of_Toronto P positive regulation of tau-protein kinase activity
GO:0032760 ISS:Alzheimers_University_of_Toronto P positive regulation of tumor necrosis factor production
GO:0017038 ISS:Alzheimers_University_of_Toronto P protein import
GO:0050821 ISS:UniProtKB P protein stabilization
GO:1900221 ISS:Alzheimers_University_of_Toronto P regulation of beta-amyloid clearance
GO:1901214 ISS:Alzheimers_University_of_Toronto P regulation of neuron death
GO:1902847 ISS:Alzheimers_University_of_Toronto P regulation of neuronal signal transduction
GO:0009416 IEP:RGD P response to light stimulus
GO:0051788 ISS:UniProtKB P response to misfolded protein
GO:0006979 IEP:RGD P response to oxidative stress
GO:0035864 IEP:RGD P response to potassium ion
GO:0009611 IEP:RGD P response to wounding
GO:0007283 IEA:UniProtKB-KW P spermatogenesis

REACTOME Pathway Links

REACTOME Pathway ID Description
5953645 Hemostasis
5953644 Platelet activation, signaling and aggregation
5954102 Platelet degranulation
5953646 Response to elevated platelet cytosolic Ca2+

Domain Information

InterPro Annotations

Accession Description
IPR016016 Clusterin
IPR016015 Clusterin, C-terminal
IPR016014 Clusterin, N-terminal
IPR000753 Clusterin-like

UniProt Annotations

Entry Information

Gene Name
clusterin
Protein Entry
CLUS_RAT
UniProt ID
P05371
Species
Rat

Comments

Comment Type Description
Developmental Stage Expressed by cells undergoing programmed death as a result of the hormonal stimuli or a traumatic insult.
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)
Ptm Extensively glycosylated with sulfated N-linked carbohydrates
Ptm Polyubiquitinated, leading to proteasomal degradation
Ptm Proteolytically cleaved on its way through the secretory system, probably within the Golgi lumen
Similarity Belongs to the clusterin family
Subcellular Location Secreted {ECO:0000269|PubMed:3415696, ECO:0000269|PubMed:3651384}. Nucleus . Cytoplasm {ECO:0000250}. Mitochondrion membrane ; Peripheral membrane protein {ECO:0000250}; Cytoplasmic side . Cytoplasm, cytosol {ECO:0000250}. Microsome . Endoplasmic reticulum . Cytoplasmic vesicle, secretory vesicle, chromaffin granule . 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)
Subunit 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)
Tissue Specificity Detected in Sertoli cells (at protein level). Detected in cultured Sertoli cells, testis, epididymis, liver and brain

Identical and Related Proteins

Unique RefSeq proteins for LMP012442 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
46048420 RefSeq NP_444180 447 clusterin precursor

Identical Sequences to LMP012442 proteins

Reference Database Accession Length Protein Name
GI:46048420 GenBank AAA41273.1 447 sulfated glycoprotein 2 precursor [Rattus norvegicus]

Related Sequences to LMP012442 proteins

Reference Database Accession Length Protein Name
GI:46048420 EMBL CAA31618.1 447 sulfated glycoprotein 2 [Rattus norvegicus]
GI:46048420 GenBank AAA41273.1 447 sulfated glycoprotein 2 precursor [Rattus norvegicus]
GI:46048420 GenBank AHH58269.1 447 Sequence 14 from patent US 8617877