Search by BoMiProt ID - Bomi10

Primary Information

BoMiProt ID Bomi10
Protein Name Clusterin
Organism Bos taurus
Uniprot IDP17697
Milk FractionWhey
Ref Sequence ID NP_776327.1
Aminoacid Length 439
Molecular Weight 51114
FASTA Sequence Download
Gene Name CLU
Gene ID 280750
Protein Existence Status Reviewed: Experimental evidence at protein level

Secondary Information

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. Clusterin (CLU) is a stress-activated, ATP-independent molecular chaperone, normally secreted from cells, that is up-regulated in Alzheimer disease and in many cancers. It plays important roles in protein homeostasis/proteostasis, inhibition of cell death pathways, and modulation of pro-survival signalling and transcriptional networks.
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;
Site(s) of PTM(s)

N-glycosylation, O-glycosylation,
Predicted Disorder Regions 73-86,432-439
DisProt Annotation
TM Helix Prediction No TM helices
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
11. Han, Z., Wang, Z., Cheng, G., Liu, B., Li, P., Li, J., … Zhang, W. (2012). Presence, localization, and origin of clusterin in normal human spermatozoa. Journal of Assisted Reproduction and Genetics, 29(8), 751–757. 12.Wilson MR, Zoubeidi A. Clusterin as a therapeutic target. Expert Opin Ther Targets. 2017 Feb;21(2):201-213. doi: 10.1080/14728222.2017.1267142. Epub 2016 Dec 16. PMID: 27978767.