Search Results
Overview
| Uniprot ID | P10909 |
|---|---|
| Protein Name | Clusterin |
| Gene Name | CLU |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 123 | CLKQTCMKFYARVCR |
| 222 | RPHFFFPKSRIVRSL |
| 299 | STGCLRMKDQCDKCR |
| 322 | TNNPSQAKLRRELDE |
| 340 | VAERLTRKYNELLKS |
| 346 | RKYNELLKSYQWKML |
| 437 | FMETVAEKALQEYRK |
| 54 | QNAVNGVKQIKTLIE |
| 57 | VNGVKQIKTLIEKTN |
| 62 | QIKTLIEKTNEERKT |
| 68 | EKTNEERKTLLSNLE |
| 78 | LSNLEEAKKKKEDAL |
Function
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:17407782, PubMed:17412999). 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: inhibits assembly of the complement membrane attack complex (MAC) by preventing polymerization of C9 pore component of the MAC complex (PubMed:2780565, PubMed:1903064, PubMed:2601725, PubMed:2721499, PubMed:1551440, PubMed:9200695, PubMed:34667172). 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 intracellular form suppresses stress-induced apoptosis by stabilizing mitochondrial membrane integrity through interaction with HSPA5 (PubMed:22689054). Secreted form does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (PubMed:24073260). Secreted form act as an important modulator during neuronal differentiation through interaction with STMN3 (By similarity). Plays a role in the clearance of immune complexes that arise during cell injury (By similarity)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Biological Process | GO:2000060 | positive regulation of ubiquitin-dependent protein catabolic process |
| Cellular Component | GO:0097440 | apical dendrite |
| Cellular Component | GO:0072562 | blood microparticle |
| Cellular Component | GO:0009986 | cell surface |
| Cellular Component | GO:0042583 | chromaffin granule |
| Cellular Component | GO:0005737 | cytoplasm |
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0070062 | extracellular exosome |
| Cellular Component | GO:0005576 | extracellular region |
| Cellular Component | GO:0005615 | extracellular space |
| Cellular Component | GO:0005794 | Golgi apparatus |
| Cellular Component | GO:0043231 | intracellular membrane-bounded organelle |
| Cellular Component | GO:0005743 | mitochondrial inner membrane |
| Cellular Component | GO:0005739 | mitochondrion |
| Cellular Component | GO:0097418 | neurofibrillary tangle |
| Cellular Component | GO:0005634 | nucleus |
| Cellular Component | GO:0099020 | perinuclear endoplasmic reticulum lumen |
| Cellular Component | GO:0048471 | perinuclear region of cytoplasm |
| Cellular Component | GO:0005886 | plasma membrane |
| Cellular Component | GO:0031093 | platelet alpha granule lumen |
| Cellular Component | GO:0032991 | protein-containing complex |
| Cellular Component | GO:0034366 | spherical high-density lipoprotein particle |
| Cellular Component | GO:0045202 | synapse |
| Molecular Function | GO:0001540 | amyloid-beta binding |
| Molecular Function | GO:0050750 | low-density lipoprotein particle receptor binding |
| Molecular Function | GO:0051787 | misfolded protein binding |
| Molecular Function | GO:0140597 | protein carrier chaperone |
| Molecular Function | GO:0140311 | protein sequestering activity |
| Molecular Function | GO:0044877 | protein-containing complex binding |
| Molecular Function | GO:0051087 | protein-folding chaperone binding |
| Molecular Function | GO:0048018 | receptor ligand activity |
| Molecular Function | GO:0005102 | signaling receptor binding |
| Molecular Function | GO:0048156 | tau protein binding |
| Molecular Function | GO:0031625 | ubiquitin protein ligase binding |
| Molecular Function | GO:0051082 | unfolded protein binding |
| Biological Process | GO:0097242 | amyloid-beta clearance |
| Biological Process | GO:0000902 | cell morphogenesis |
| Biological Process | GO:0032286 | central nervous system myelin maintenance |
| Biological Process | GO:0051131 | chaperone-mediated protein complex assembly |
| Biological Process | GO:0006956 | complement activation |
| Biological Process | GO:0006958 | complement activation, classical pathway |
| Biological Process | GO:0002434 | immune complex clearance |
| Biological Process | GO:0045087 | innate immune response |
| Biological Process | GO:0097193 | intrinsic apoptotic signaling pathway |
| Biological Process | GO:0006629 | lipid metabolic process |
| Biological Process | GO:0001774 | microglial cell activation |
| Biological Process | GO:0061518 | microglial cell proliferation |
| Biological Process | GO:0001971 | negative regulation of activation of membrane attack complex |
| Biological Process | GO:1905907 | negative regulation of amyloid fibril formation |
| Biological Process | GO:1902430 | negative regulation of amyloid-beta formation |
| Biological Process | GO:0045916 | negative regulation of complement activation |
| Biological Process | GO:1903660 | negative regulation of complement-dependent cytotoxicity |
| Biological Process | GO:1902230 | negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage |
| Biological Process | GO:0043524 | negative regulation of neuron apoptotic process |
| Biological Process | GO:0031333 | negative regulation of protein-containing complex assembly |
| Biological Process | GO:0090201 | negative regulation of release of cytochrome c from mitochondria |
| Biological Process | GO:1903573 | negative regulation of response to endoplasmic reticulum stress |
| Biological Process | GO:1905908 | positive regulation of amyloid fibril formation |
| Biological Process | GO:1902004 | positive regulation of amyloid-beta formation |
| Biological Process | GO:0043065 | positive regulation of apoptotic process |
| Biological Process | GO:0010628 | positive regulation of gene expression |
| Biological Process | GO:2001244 | positive regulation of intrinsic apoptotic signaling pathway |
| Biological Process | GO:1902998 | positive regulation of neurofibrillary tangle assembly |
| Biological Process | GO:0045429 | positive regulation of nitric oxide biosynthetic process |
| Biological Process | GO:0032436 | positive regulation of proteasomal ubiquitin-dependent protein catabolic process |
| Biological Process | GO:0031334 | positive regulation of protein-containing complex assembly |
| Biological Process | GO:0048260 | positive regulation of receptor-mediated endocytosis |
| Biological Process | GO:0032760 | positive regulation of tumor necrosis factor production |
| Biological Process | GO:0006457 | protein folding |
| Biological Process | GO:0017038 | protein import |
| Biological Process | GO:0050821 | protein stabilization |
| Biological Process | GO:0061740 | protein targeting to lysosome involved in chaperone-mediated autophagy |
| Biological Process | GO:1900221 | regulation of amyloid-beta clearance |
| Biological Process | GO:0042981 | regulation of apoptotic process |
| Biological Process | GO:0042127 | regulation of cell population proliferation |
| Biological Process | GO:1902847 | regulation of neuronal signal transduction |
| Biological Process | GO:0001836 | release of cytochrome c from mitochondria |
| Biological Process | GO:0051788 | response to misfolded protein |
| Biological Process | GO:0009615 | response to virus |
| Biological Process | GO:0043691 | reverse cholesterol transport |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.
[3] Lin Y, Chen M, Wang D, Yu Y, Chen R et al.. Multi-Proteomic Analysis Reveals the Effect of Protein Lactylation on Matrix and Cholesterol Metabolism in Tendinopathy.. J Proteome Res 22(6):1712-1722. 2023 Jun 2. PMID: 37159428.
[4] Yan M, Tu H, Tang S, Gai Z, Shi Q et al.. Lactylated Proteomic Analysis Reveals Functional Implications of Lysine Lactylation In Asthenozoospermia.. Mol Cell Proteomics 24(12):101439. 2025 Dec. PMID: 41192556.