|Ref Sequence Id||NP_776327.1|
|Amino Acid Lenth||439|
|Protein Existence Status||Reviewed: Experimental evidence at protein level|
|Presence in other biological fluids/tissue/cells||normal human spermatozoa ; In normal human lung,fibroblast-like cells and sporadic areas of bronchial epithelial cells|
|Protein Function||Important roles in immune regulation, ageing, tissue remodeling, lipid transport, membrane recycling, complements cascade, DNA repair, cell adhesion, and cell-cell interactions, cancer progression, vascular damage, diabetes, kidney and neuron degeneration; protects cells against cytotoxic agents that induce apoptosis, and acts as a pro-death signal, inhibiting cell growth and survival|
|Biochemical Properties||exhibit chaperone-like activity and prevents the chemically-induced and heat-induced amorphous aggregation as well as amyloid aggregation; full-length clusterin binds to client proteins through the hydrophobic patches present on the protein and chaperones them from aggregation; far-UV CD spectra of α -Clu and β -Clu are very similar and exhibit minima at 218 nm and 208 nm; fluorescence emission spectra of α -Clu and β -Clu upon excitation at 295 nm exhibit emission maximum at 333 nm and 338 nm respectively; tryptophan residues in both proteins are in a hydrophobic environment, the tryptophans in α -Clu being in a slightly more hydrophobic environment than those in β -Clu; α -Clu exhibits a distinct peak with a sedimentation coefficient of 36.8 S|
|Significance in milk||more abundant in human milk than in bovine milk; most abundant proteins in the human MFGM fraction; linked to cell damage and apoptosis and has been shown to be overexpressed at damaged or stressed tissues and to provide a chaperone-like activity to protect other proteins against damage|
|PTMs||heavy glycosylation; carbohydrate comprises approximately 20-25% of the total mass of the mature molecule; six N-linked glycosylation sites have been identified, three in the alpha chain (α64N, α81N, and α123N) and three in the beta chain (ß64N, ß127N, and ß147N); types of oligosaccharides attached to the clusterin peptide are diverse;|
|Significance of PTMs||hydrophilic carbohydrate moieties might enhance the chaperone action of clusterin by helping it keep such complexes in solution|
|Additional Comments||mutations in the protein might lead to its altered localization and functions in the cell|
|Bibliography||1. Yang, Y., Bu, D., Zhao, X., Sun, P., Wang, J., & Zhou, L. (2013). Proteomic analysis of cow, yak, buffalo, goat and camel milk whey proteins: quantitative differential expression patterns. Journal of Proteome Research, 12(4), 1660–1667. https://doi.org/10.1021/pr301001m. |
2. Xiu, P., Dong, X., Dong, X., Xu, Z., Zhu, H., Liu, F., … Sun, X. (2013). Secretory clusterin contributes to oxaliplatin resistance by activating Akt pathway in hepatocellular carcinoma. Cancer Science, 104(3), 375–382. https://doi.org/10.1111/cas.12088.
3. Hettinga, K., van Valenberg, H., de Vries, S., Boeren, S., van Hooijdonk, T., van Arendonk, J., & Vervoort, J. (2011). The host defense proteome of human and bovine milk. PloS One, 6(4), e19433. https://doi.org/10.1371/journal.pone.0019433.
4. Lambert, J.-C., Heath, S., Even, G., Campion, D., Sleegers, K., Hiltunen, M., … Amouyel, P. (2009). Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nature Genetics, 41(10), 1094–1099. https://doi.org/10.1038/ng.439.
5. Stewart, E. M., Aquilina, J. A., Easterbrook-Smith, S. B., Murphy-Durland, D., Jacobsen, C., Moestrup, S., & Wilson, M. R. (2007). Effects of glycosylation on the structure and function of the extracellular chaperone clusterin. Biochemistry, 46(5), 1412–1422. https://doi.org/10.1021/bi062082v.
6. Wang, X., Zou, F., Zhong, J., Yue, L., Wang, F., Wei, H., … Xiu, P. (2018). Secretory Clusterin Mediates Oxaliplatin Resistance via the Gadd45a/PI3K/Akt Signaling Pathway in Hepatocellular Carcinoma. Journal of Cancer, 9(8), 1403–1413. https://doi.org/10.7150/jca.23849.
7. Zhong, J., Yu, X., Dong, X., Lu, H., Zhou, W., Li, L., … Shi, X. (2018). Downregulation of secreted clusterin potentiates the lethality of sorafenib in hepatocellular carcinoma in association with the inhibition of ERK1/2 signals. International Journal of Molecular Medicine, 41(5), 2893–2900. https://doi.org/10.3892/ijmm.2018.3463.
8. Wang, C., Jiang, K., Kang, X., Gao, D., Sun, C., Li, Y., … Liu, Y. (2012). Tumor-derived secretory clusterin induces epithelial-mesenchymal transition and facilitates hepatocellular carcinoma metastasis. The International Journal of Biochemistry & Cell Biology, 44(12), 2308–2320. https://doi.org/10.1016/j.biocel.2012.09.012.
9. Trougakos, I. P., & Gonos, E. S. (2006). Regulation of clusterin/apolipoprotein J, a functional homologue to the small heat shock proteins, by oxidative stress in ageing and age-related diseases. Free Radical Research, 40(12), 1324–1334. https://doi.org/10.1080/10715760600902310.
10. Lourda, M., Trougakos, I. P., & Gonos, E. S. (2007). Development of resistance to chemotherapeutic drugs in human osteosarcoma cell lines largely depends on up-regulation of Clusterin/Apolipoprotein J. International Journal of Cancer, 120(3), 611–622. https://doi.org/10.1002/ijc.22327.
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