The CLU domain (CLUstered mitochondria) is a eukaryotic domain found in highly conserved eukaryotic proteins required for correct mitochondrial dispersal [, ]. The exact function of the domain is unknown [].
Mutations in the mitochondrial CLU proteins have been shown to result in clustered mitochondria [, , ]. CLU proteins include Saccharomyces cerevisiae clustered mitochondria protein (Clu1p, alias translation initiation factor 31/TIF31p), Dictyostelium discoideum clustered mitochondria protein homologue (CluA), Caenorhabditis elegans clustered mitochondria protein homologue (CLUH/ Protein KIAA0664), Drosophila clueless (alias clustered mitochondria protein homologue), Arabidopsis clustered mitochondria protein (CLU, alias friendly mitochondria protein/FMT), and human clustered mitochondria protein homologue (CLUH).Dictyostelium CluA is involved in mitochondrial dynamics and is necessary for both, mitochondrial fission and fusion []. Drosophila clueless is essential for cytoplasmic localization and function of cellular mitochondria []. The Drosophila clu gene interacts genetically with parkin (park, the Drosophila ortholog of a human gene responsible for many familial cases of Parkinson's disease) []. Arabidopsis CLU/FMT is required for correct mitochondrial distribution and morphology []. The specific role CLU proteins play in mitochondrial processes in not yet known. In an early study, S. cerevisiae Clu1/TIF31p was reported as sometimes being associated with the elF3 translation initiation factor. The authors noted, however, that its tentative assignment as a subunit of elf3 was uncertain, and to date there has been no direct evidence for a role of this protein in translation [].This entry represents a central domain in CLU proteins.
This entry includes protein clueless from Drosophila, Clu1 from yeasts and protein CLU from plants. They are involved in proper cytoplasmic distribution of mitochondria [, ].Protein clueless from Drosophila is required for mitochondrial subcellular localisation, interacts genetically with parkin []. It is highly expressed in larval neuroblasts, affects mitochondrial localisation and suppresses mitochondrial oxidative damage [].Budding yeast Clu1 is a subunit of the eukaryotic translation initiation factor3 (eIF3). It can influence mitochondrial morphology and distribution []. Arabidopsis CLU, also known as FRIENDLY (At3g52140), is involved in regulating intermitochondrial association, a prelude to mitochondria fusion [, ]. FRIENDLY may have expanded into a small gene family to help manage the energy metabolism of cells that contain both chloroplasts and mitochondria. These homologue are known as REDUCED CHLOROPLAST COVERAGE (REC) 1/2/3 (AT1G01320 , AT4G28080, AT1G15290). Together, they contribute to establishing the size of the chloroplast compartment [].
Clusterin (Clu), also known as apolipoprotein J, is a vertebrate glycoprotein []. Clusterin expression is complex, appearing as different forms indifferent cell compartments. One set of proteins is directed for secretion, and other clusterin species are expressed in thecytoplasm and nucleus. The secretory form of the clusterin protein (sCLU) is targeted to the ER by an initial leader peptide. This ~60kDa pre-sCLU protein is proteolytically cleaved into alpha- and beta-subunits and further glycosylated to form mature disulfide-linked heterodimeric secretory CLU (sCLU). sCLU is an 80kDa protein and acts as a molecular chaperone, scavenging denatured proteins outside cells [, ]. sCLU possesses nonspecific binding activity to hydrophobic domains of various non-native proteins [], binds to some bacteria and bacterial proteins [], and interacts with different immune molecules [].A specific nuclear form of CLU (nCLU) acts as a pro-death signal, inhibiting cell growth andsurvival. ThenCLU protein has two coiled-coil domains, one at its N terminus that is unable to bind Ku70, and a C-terminal coiled-coil domain that is uniquely able to associatewith Ku70 and is minimally required forcell death. The sCLU protein is cytoprotective and anti-apoptotic, whereas the nCLU protein is pro-apoptotic [, , ].
Clusterin (Clu), also known as apolipoprotein J, is a vertebrate glycoprotein []. Clusterin expression is complex, appearing as different forms indifferent cell compartments. One set of proteins is directed for secretion, and other clusterin species are expressed in thecytoplasm and nucleus. The secretory form of the clusterin protein (sCLU) is targeted to the ER by an initial leader peptide. This ~60kDa pre-sCLU protein is proteolytically cleaved into alpha- and beta-subunits and further glycosylated to form mature disulfide-linked heterodimeric secretory CLU (sCLU). sCLU is an 80kDa protein and acts as a molecular chaperone, scavenging denatured proteins outside cells [, ]. sCLU possesses nonspecific binding activity to hydrophobic domains of various non-native proteins [], binds to some bacteria and bacterial proteins [], and interacts with different immune molecules [].A specific nuclear form of CLU (nCLU) acts as a pro-death signal, inhibiting cell growth andsurvival. ThenCLU protein has two coiled-coil domains, one at its N terminus that is unable to bind Ku70, and a C-terminal coiled-coil domain that is uniquely able to associatewith Ku70 and is minimally required for cell death. The sCLU protein is cytoprotective and anti-apoptotic, whereas the nCLU protein is pro-apoptotic [, , ].This family also includes clusterin-like protein 1 (CLUL1), which is expressed specifically in cone photoreceptor cells []and is likely to be necessary for normal cone function [].
Clusterin is a vertebrate glycoprotein [], the exact function of which is not yet clear. Clusterin expression is complex, appearing as different forms indifferent cell compartments. One set of proteins is directed for secretion, and other clusterin species are expressed in thecytoplasm and nucleus. The secretory form of the clusterin protein (sCLU) is targeted to the ER by an initialleader peptide. This ~60kDa pre-sCLU protein is further glycosylated and proteolytically cleaved into alpha- and beta-subunits, held together by disulphide bonds.External sCLU is an 80kDa protein and may act as a molecular chaperone, scavenging denatured proteins outside cells following specific stress-induced injury such as heat shock. sCLU possesses nonspecific binding activity to hydrophobic domains of various proteins in vitro[].A specific nuclear form of CLU (nCLU) acts as a pro-death signal, inhibiting cell growth andsurvival. ThenCLU protein has two coiled-coil domains, one at its N terminus that is unable to bind Ku70, and a C-terminal coiled-coil domain that is uniquely able to associatewith Ku70 and is minimally required for cell death.Clusterin is synthesized as a precursor polypeptide of about 400 amino acids which is post-translationally cleaved to form two subunits of about 200 amino acids each. The two subunits are linked by five disulphide bonds to form anantiparallel ladder-like structure []. In each of the mature subunits the five cysteines that are involved in disulphide bonds are clustered in domains of about 30 amino acids located in the central part of the subunits.This entry represents the N-terminal domain of the clusterin precursor.
Clusterin is a vertebrate glycoprotein [], the exact function of which is not yet clear. Clusterinexpression is complex, appearing as different forms indifferent cell compartments. One set of proteins is directed for secretion, and other clusterin species are expressed in thecytoplasm and nucleus. The secretory form of the clusterin protein (sCLU) is targeted to the ER by an initialleader peptide. This ~60kDa pre-sCLU protein is further glycosylated and proteolytically cleaved into alpha- and beta-subunits, held together by disulphide bonds.External sCLU is an 80kDa protein and may act as a molecular chaperone, scavenging denatured proteins outside cells following specific stress-induced injury such as heat shock. sCLU possesses nonspecific binding activity to hydrophobic domains of various proteins in vitro[].A specific nuclear form of CLU (nCLU) acts as a pro-death signal, inhibiting cell growth andsurvival. ThenCLU protein has two coiled-coil domains, one at its N terminus that is unable to bind Ku70, and a C-terminal coiled-coil domain that is uniquely able to associatewith Ku70 and is minimally required for cell death.Clusterin is synthesized as a precursor polypeptide of about 400 amino acids which is post-translationally cleaved to form two subunits of about 200 amino acids each. The two subunits are linked by five disulphide bonds to form anantiparallel ladder-like structure []. In each of the mature subunits the five cysteines that are involved in disulphide bonds are clustered in domains of about 30 amino acids located in the central part of the subunits.This entry represents the C-terminal domain of the custerin precursor.
