Clusterin (CLU)
The protein contains 449 amino acids for an estimated molecular weight of 52495 Da.
Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922, PubMed:12176985, PubMed:17260971, PubMed:19996109). Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro) (PubMed:12047389, PubMed:17412999, PubMed:17407782). Does not require ATP (PubMed:11123922). Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70 (PubMed:11123922). Does not refold proteins by itself (PubMed:11123922). Binding to cell surface receptors triggers internalization of the chaperone-client complex and subsequent lysosomal or proteasomal degradation (PubMed:21505792). Protects cells against apoptosis and against cytolysis by complement (PubMed:2780565). 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 (PubMed:20068069). Promotes proteasomal degradation of COMMD1 and IKBKB (PubMed:20068069). Modulates NF-kappa-B transcriptional activity (PubMed:12882985). A mitochondrial form suppresses BAX-dependent release of cytochrome c into the cytoplasm and inhibit apoptosis (PubMed:16113678, PubMed:17689225). Plays a role in the regulation of cell proliferation (PubMed:19137541). An (updated: Dec. 11, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs9331936 | |
| dbSNP:rs9331938 | |
| dbSNP:rs13494 |
Biological Process
Antimicrobial humoral response
Blood coagulation
Cell morphogenesis
Central nervous system myelin maintenance
Chaperone-mediated protein complex assembly
Chaperone-mediated protein folding
Complement activation
Complement activation, classical pathway
Immune complex clearance
Innate immune response
Intrinsic apoptotic signaling pathway
Lipid metabolic process
Microglial cell activation
Microglial cell proliferation
Negative regulation of amyloid fibril formation
Negative regulation of amyloid-beta formation
Negative regulation of cell death
Negative regulation of cellular response to thapsigargin
Negative regulation of cellular response to tunicamycin
Negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage
Negative regulation of protein homooligomerization
Negative regulation of protein-containing complex assembly
Negative regulation of release of cytochrome c from mitochondria
Negative regulation of response to endoplasmic reticulum stress
Obsolete chaperone-mediated protein transport involved in chaperone-mediated autophagy
Platelet activation
Platelet degranulation
Positive regulation of amyloid fibril formation
Positive regulation of amyloid-beta formation
Positive regulation of apoptotic process
Positive regulation of gene expression
Positive regulation of intrinsic apoptotic signaling pathway
Positive regulation of neurofibrillary tangle assembly
Positive regulation of neuron death
Positive regulation of NF-kappaB transcription factor activity
Positive regulation of nitric oxide biosynthetic process
Positive regulation of proteasomal ubiquitin-dependent protein catabolic process
Positive regulation of protein homooligomerization
Positive regulation of protein-containing complex assembly
Positive regulation of receptor-mediated endocytosis
Positive regulation of tau-protein kinase activity
Positive regulation of tumor necrosis factor production
Positive regulation of ubiquitin-dependent protein catabolic process
Protein import
Protein stabilization
Protein targeting to lysosome involved in chaperone-mediated autophagy
Regulation of amyloid-beta clearance
Regulation of apoptotic process
Regulation of cell population proliferation
Regulation of complement activation
Regulation of neuron death
Regulation of neuronal signal transduction
Release of cytochrome c from mitochondria
Response to misfolded protein
Response to virus
Reverse cholesterol transport
Cellular Component
Apical dendrite
Blood microparticle
Cell surface
Chromaffin granule
Collagen-containing extracellular matrix
Cytoplasm
Cytosol
Endoplasmic reticulum
Extracellular exosome
Extracellular matrix
Extracellular region
Extracellular space
Golgi apparatus
Intracellular anatomical structure
Intracellular membrane-bounded organelle
Mitochondrial inner membrane
Mitochondrial membrane
Mitochondrion
Neurofibrillary tangle
Nucleus
Perinuclear endoplasmic reticulum lumen
Perinuclear region of cytoplasm
Platelet alpha granule lumen
Protein complex
Protein-containing complex
Spherical high-density lipoprotein particle
Synapse
Molecular Function
Amyloid-beta binding
Chaperone binding
Low-density lipoprotein particle receptor binding
Misfolded protein binding
Protein complex binding
Protein heterodimerization activity
Protein-containing complex binding
Signaling receptor binding
Tau protein binding
Ubiquitin protein ligase binding
Unfolded protein binding
The reference OMIM entry for this protein is 185430
Clusterin; clu
Sulfated glycoprotein 2; sgp2
Apolipoprotein j; apoj
Complement-associated protein sp-40,40
Complement lysis inhibitor; cli
Testosterone-repressed prostate message 2; trpm2
CLONING
Murphy et al. (1988) described a novel serum protein, SP-40,40, using a series of monoclonal antibodies directed to the immune deposit-containing glomerular basement membranes of a patient with membranous glomerulonephritis. The protein was shown to be a normal constituent of human blood. It consists of two 40-kD chains, alpha and beta, covalently joined by disulfide bonds. They established that SP-40,40 is a member of the human complement system by directly demonstrating its presence within the S-protein-containing soluble variant of the C5b-9 complex, SC5b-9. SP-40,40 is also called complement lysis inhibitor or clusterin. It acts as a control mechanism of the complement cascade; specifically, it prevents the binding of a C5b-C7 complex to the membrane of the target cell and in this way inhibits complement-mediated cytolysis. Kirszbaum et al. (1989) cloned a cDNA for the SP-40,40 protein. They showed that the 2 chains are coded in a single open reading frame on the same mRNA molecule, indicating that a precursor protein matures postsynthetically by the proteolysis of at least 1 peptide bond. They found that the sequence of the SP-40,40 precursor has 77% identity with rat sulfated glycoprotein-2 (SGP2), which is the major secreted product of Sertoli cells. They demonstrated the presence of SP-40,40 within human seminal plasma at levels comparable to those in serum, indicating that SP-40,40 and SGP2 are serum and seminal forms of the same protein. A sequence of 23 amino acids within the beta-chain of SP-40,40 showed significant homology to corresponding segments in C7, C8, and C9. The findings of Kirszbaum et al. (1989) document a link between the immune and reproductive systems. O'Bryan et al. (1990) reported the purification and characterization of human seminal clusterin. There is reason to think that testosterone-repressed prostate message-2 is coded by the same gene (Purrello et al., 1991). Comparison of the multiple functions suggests involvement of this protein in the cascade of events leading to programmed cell death. Apolipoprotein J is another name for the human analog of the rat protein SGF2. Its primary structure was deduced by de Silva et al. (1990) using the combined strategies of protein sequencing and cDNA cloning and sequencing. It is a 70-kD protein associated with high-density lipoproteins (HDL) in human plasma. There is a single copy of the APOJ gene in the human and mouse genomes. The protein is synthesized as a 427-amino acid polypeptide that is posttranslationally cleaved at an internal bond between arg205 and ser206. Two subunits, designated alpha (34 to 36 kD), corresponding to residues 1-205, and beta (36 to 39 kD), corresponding to residues 206-427, are associated through disulfide bonds. Studies indicated that the alpha and beta subunits are derived from a common precursor by proteolytic cleavage and that the subunits, while distinct, have limited regions of homology. De Silva et al. (1990) found APOJ mRNA (1.9 kb) in all but one tissue examined. Its concentration was relatively high in brain, ovary, testis, and liver, lower in heart, spleen, lung, and breast, and absent in T lymphocytes. Apolipoprotein J is distinct from other known apolipoproteins in molecular weight, subunit structure, and isoelectric point.MAPPING
By Southern analysis of somatic cell hybrids, Purrello et al. (1991) concluded that a single gene is responsible for the multiple functions of sulfated glycoprotei ... More on the omim web site
Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
June 7, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 185430 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed