Recombinant Human Klotho (aa 34-981) Protein, CF

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5334-KL-025
R&D Systems Recombinant Proteins and Enzymes
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Recombinant Human Klotho (aa 34-981) Protein, CF Summary

Product Specifications

Purity
>90%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining
Endotoxin Level
<1.0 EU per 1 μg of the protein by the LAL method.
Activity
Measured in a cell proliferation assay using BaF3 mouse pro‑B cells transfected with human FGF RIIIc. The ED50 for this effect is 0.025-0.1 μg/mL in the presence of Recombinant Human FGF‑23 (Catalog # 2604-FG) and Heparin.
Source
Mouse myeloma cell line, NS0-derived human Klotho protein
Glu34-Ser981, with a C-terminal 6-His tag
Accession #
N-terminal Sequence
Analysis
Glu34
Predicted Molecular Mass
109.8 kDa
SDS-PAGE
120-130 kDa, reducing conditions

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5334-KL

Carrier Free

What does CF mean?

CF stands for Carrier Free (CF). We typically add Bovine Serum Albumin (BSA) as a carrier protein to our recombinant proteins. Adding a carrier protein enhances protein stability, increases shelf-life, and allows the recombinant protein to be stored at a more dilute concentration. The carrier free version does not contain BSA.

What formulation is right for me?

In general, we advise purchasing the recombinant protein with BSA for use in cell or tissue culture, or as an ELISA standard. In contrast, the carrier free protein is recommended for applications, in which the presence of BSA could interfere.

5334-KL

Formulation Supplied as a 0.2 μm filtered solution in MES, Glycerol and EDTA.
Shipping The product is shipped with dry ice or equivalent. Upon receipt, store it immediately at the temperature recommended below.
Stability & Storage: Use a manual defrost freezer and avoid repeated freeze-thaw cycles.
  • 12 months from date of receipt, -70 °C as supplied.
  • 1 month, 2 to 8 °C under sterile conditions after opening.
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Background: Klotho

Klotho, also called Klotho-alpha, is the founding member of the Klotho family within the glycosidase-1 superfamily (1, 2). Klotho is expressed in areas concerned with calcium regulation, predominantly in the kidney distal convoluted tubules, but also in the brain choroid plexus (which produces cerebrospinal fluid) and the parathyroid (1). The 1012 amino acid (aa) type I transmembrane protein contains a 32 aa signal sequence, a 948 aa extracellular domain (ECD) containing two extracellular glycosidase-like domains, a 21 aa transmembrane domain and a 10 aa intracellular domain. Within the ECD, human Klotho shares 87%, 90%, 90% and 86% aa identity with mouse, rat, bovine and equine Klotho, respectively. A 130 kDa form found in plasma and cerebrospinal fluid is produced by proteolytic cleavage of the glycosylated 135 kDa full-length Klotho (3, 4). A truncated 549 aa isoform predicted by alternative mRNA splicing has been detected in human and mice (3, 4). A prominent intracellular 120 kDa form of Klotho is localized to endoplasmic reticulum and Golgi membranes (4). The phenotype of Klotho-deficient mice resembles premature aging, including arteriosclerosis, osteoporosis, skin atrophy, infertility, emphysema and premature death (2). Conversely, excess Klotho extends lifespan (5). Klotho acts as a cofactor for interaction of FGF-23 with FGF R1 (6). This interaction negatively regulates 1 alpha -hydroxylase, the rate-limiting enzyme in the synthesis of 1,25(OH)2D3 (vitamin D) (7). Klotho deficient mice show severe hyperphosphatemia and ectopic calcification of soft tissues due to excess vitamin D
(2-7). Both Klotho and Klotho beta are cofactors for FGF19 binding (8). Klotho also shows glucuronidase activity which activates the renal ion channel TRPV5 to reabsorb urinary calcium (9). Klotho has been reported to downregulate insulin or IGF-1 signaling in adipocytes, to bind and antagonize Wnt molecules, and to facilitate release of parathyroid hormone (10-12).

References
  1. Nabeshima, Y. (2006) Sci. Aging Knowl. Environ. 8:pe11.
  2. Kuro-o, M. et al. (1997) Nature 390:45.
  3. Shiraki-Iida, T. et al. (1998) FEBS Lett. 424:6.
  4. Imura, A. et al. (2004) FEBS Lett. 565:143.
  5. Kurosu, H. et al. (2005) Science 309:1829.
  6. Kurosu, H. et al. (2006) J. Biol. Chem. 281:6120.
  7. Tsujikawa, H. et al. (2003) Mol. Endocrinol. 17:2393.
  8. Wu, X. et al. (2007) J. Biol. Chem. 282:29069.
  9. Chang, Q. et al. (2005) Science 310:490.
  10. Yamamoto, M. et al. (2005) J. Biol. Chem. 280:38029.
  11. Liu, H. et al. (2007) Science 317:803.
  12. Imura, A. et al. (2007) Science 316:1615.
Entrez Gene IDs
9365 (Human); 16591 (Mouse)
Alternate Names
EC 3.2.1; EC 3.2.1.31; KL; Klotho

Citations for Recombinant Human Klotho (aa 34-981) Protein, CF

R&D Systems personnel manually curate a database that contains references using R&D Systems products. The data collected includes not only links to publications in PubMed, but also provides information about sample types, species, and experimental conditions.

23 Citations: Showing 1 - 10
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  1. Klotho Protein Decreases MMP-Mediated Degradation of Contractile Proteins during Ischaemia/Reperfusion Injury to the Cardiomyocytes
    Authors: A Olejnik, A Krzywonos-, M Banaszkiew, I Bil-Lula
    International Journal of Molecular Sciences, 2022;23(24):.
    Species: Human
    Sample Types: Whole Cells
    Applications: Bioassay
  2. Renal Klotho and inorganic phosphate are extrinsic factors that antagonistically regulate hematopoietic stem cell maintenance
    Authors: C Du, X Wang, Y Wu, W Liao, J Xiong, Y Zhu, C Liu, W Han, Y Wang, S Han, S Chen, Y Xu, S Wang, F Wang, K Yang, J Zhao, J Wang
    Cell Reports, 2022;38(7):110392.
    Species: Human
    Sample Types: Whole Cells
    Applications: Bioassay
  3. Klotho retards renal fibrosis through targeting mitochondrial dysfunction and cellular senescence in renal tubular cells
    Authors: J Miao, J Huang, C Luo, H Ye, X Ling, Q Wu, W Shen, L Zhou
    Physiological Reports, 2021;9(2):e14696.
    Species: Human
    Sample Types: Whole Cells
    Applications: Bioassay
  4. Protective effects of klotho on palmitate-induced podocyte injury in diabetic nephropathy
    Authors: J Suk Kang, SS Son, JH Lee, SW Lee, AR Jeong, ES Lee, SK Cha, CH Chung, EY Lee
    PLoS ONE, 2021;16(4):e0250666.
    Species: Mouse
    Sample Types: Whole Cells
    Applications: Bioassay
  5. A novel antibody for the detection of alternatively spliced secreted KLOTHO isoform in human plasma
    Authors: S Jadhav, S Tripathi, A Chandrekar, SS Waikar, LL Hsiao
    PLoS ONE, 2021;16(1):e0245614.
    Species: Human
    Sample Types: Protein
    Applications: ELISA Capture
  6. Klotho Alleviates Lung Injury Caused by Paraquat via Suppressing ROS/P38 MAPK-Regulated Inflammatory Responses and Apoptosis
    Authors: Z Zhang, Q Nian, G Chen, S Cui, Y Han, J Zhang
    Oxid Med Cell Longev, 2020;2020(0):1854206.
    Species: Human
    Sample Types: Whole Cells
    Applications: Bioassay
  7. Mechanistic Roles of Matrilin-2 and Klotho in Modulating the Inflammatory Activity of Human Aortic Valve Cells
    Authors: E The, Q Yao, P Zhang, Y Zhai, L Ao, DA Fullerton, X Meng
    Cells, 2020;9(2):.
    Species: Human
    Sample Types: Whole Cells
    Applications: Cell Culture
  8. Salt causes aging-associated hypertension via vascular Wnt5a under Klotho deficiency
    Authors: W Kawarazaki, R Mizuno, M Nishimoto, N Ayuzawa, D Hirohama, K Ueda, F Kawakami-M, S Oba, T Marumo, T Fujita
    J. Clin. Invest., 2020;0(0):.
    Species: Human
    Sample Types: Whole Cells
    Applications: Cell Culture
  9. Soluble Klotho, a biomarker and therapeutic strategy to reduce bronchopulmonary dysplasia and pulmonary hypertension in preterm infants
    Authors: S Batlahally, A Franklin, A Damianos, J Huang, P Chen, M Sharma, J Duara, D Keerthy, R Zambrano, LA Shehadeh, EC Martinez, MJ DeFreitas, S Kulandavel, CL Abitbol, M Freundlich, RM Kanashiro-, A Schmidt, M Benny, S Wu, KK Mestan, KC Young
    Sci Rep, 2020;10(1):12368.
    Species: Human
    Sample Types: Whole Cell
    Applications: Bioassay
  10. Klotho protein contributes to cardioprotection during ischaemia/reperfusion injury
    Authors: A Olejnik, A Krzywonos-, M Banaszkiew, I Bil-Lula
    J. Cell. Mol. Med., 2020;0(0):.
    Species: Human
    Sample Types: Whole Cells
    Applications: Bioassay
  11. Urinary Extracellular Vesicles Carrying Klotho Improve the Recovery of Renal Function in an Acute Tubular Injury Model
    Authors: C Grange, E Papadimitr, V Dimuccio, C Pastorino, J Molina, R O'Kelly, LJ Niedernhof, PD Robbins, G Camussi, B Bussolati
    Mol. Ther., 2019;0(0):.
    Species: Human
    Sample Types: Extracellular Vesicles
    Applications: Cell Culture
  12. Wnt/?-catenin/RAS signaling mediates age-related renal fibrosis and is associated with mitochondrial dysfunction
    Authors: J Miao, J Liu, J Niu, Y Zhang, W Shen, C Luo, Y Liu, C Li, H Li, P Yang, Y Liu, FF Hou, L Zhou
    Aging Cell, 2019;0(0):e13004.
    Species: Human
    Sample Types: Whole Cells
    Applications: Bioassay
  13. Age-related declines in ?-Klotho drive progenitor cell mitochondrial dysfunction and impaired muscle regeneration
    Authors: A Sahu, H Mamiya, SN Shinde, A Cheikhi, LL Winter, NV Vo, D Stolz, V Roginskaya, WY Tang, C St Croix, LH Sanders, M Franti, B Van Houten, TA Rando, A Barchowsky, F Ambrosio
    Nat Commun, 2018;9(1):4859.
    Species: Mouse
    Sample Types: Whole Cells
    Applications: Bioassay
  14. Klotho suppresses colorectal cancer through modulation of the unfolded protein response
    Authors: T Arbel Rubi, S Shahmoon, E Zigmond, T Etan, K Merenbakh-, M Pasmanik-C, G Har-Zahav, I Barshack, GW Vainer, N Skalka, R Rosin-Arbe, C Varol, T Rubinek, I Wolf
    Oncogene, 2018;0(0):.
    Species: Human
    Sample Types: Whole Cells
    Applications: Bioassay
  15. Klotho enhances FoxO3-mediated manganese superoxide dismutase expression by negatively regulating PI3K/AKT pathway during tacrolimus-induced oxidative stress
    Authors: SW Lim, L Jin, K Luo, J Jin, YJ Shin, SY Hong, CW Yang
    Cell Death Dis, 2017;8(8):e2972.
    Species: Human
    Sample Types: Whole Cells
    Applications: Bioassay
  16. Soluble klotho binds monosialoganglioside to regulate membrane microdomains and growth factor signaling
    Authors: G Dalton, SW An, SI Al-Juboori, N Nischan, J Yoon, E Dobrinskik, DW Hilgemann, J Xie, K Luby-Phelp, JJ Kohler, L Birnbaumer, CL Huang
    Proc. Natl. Acad. Sci. U.S.A, 2017;114(4):752-757.
    Species: Human
    Sample Types: Whole Cells
    Applications: Bioassay
  17. Klotho ameliorates oxidized low density lipoprotein (ox-LDL)-induced oxidative stress via regulating LOX-1 and PI3K/Akt/eNOS pathways
    Authors: Y Yao, Y Wang, Y Zhang, C Liu
    Lipids Health Dis, 2017;16(1):77.
    Species: Human
    Sample Types: Whole Cells
    Applications: Bioassay
  18. Inhibition of age-related therapy resistance in melanoma by rosiglitazone-mediated induction of Klotho
    Authors: R Behera, A Kaur, MR Webster, S Kim, A Ndoye, CH Kugel, GM Alicea, JX Wang, K Ghosh, PF Cheng, S Lisanti, K Marchbank, V Dang, MP Levesque, R Dummer, X Xu, M Heryn, AE Aplin, A Roesch, MC Caino, DC Altieri, AT Weeraratna
    Clin. Cancer Res, 2017;0(0):.
    Species: Human
    Sample Types: Whole Cells
    Applications: Bioassay
  19. Epigallocatechin-3-O-(3-O-methyl)-gallate-induced differentiation of human keratinocytes involves klotho-mediated regulation of protein kinase-cAMP responsive element-binding protein signaling.
    Authors: Kim H, Chang H, Han S, Lee M, Jung J, An S, Baek S, Lee J, Lee J, Lee T, Shin D, Kim H
    Int J Mol Sci, 2014;15(4):5749-61.
    Species: Human
    Sample Types: Whole Cells
    Applications: Bioassay
  20. The aging suppressor klotho: a potential regulator of growth hormone secretion.
    Authors: Shahmoon S, Rubinfeld H, Wolf I, Cohen Z, Hadani M, Shimon I, Rubinek T
    Am J Physiol Endocrinol Metab, 2014;307(3):E326-34.
    Species: Human
    Sample Types: Whole Cells
    Applications: Bioassay
  21. Direct, acute effects of Klotho and FGF23 on vascular smooth muscle and endothelium.
    Authors: Six I, Okazaki H, Gross P, Cagnard J, Boudot C, Maizel J, Drueke T, Massy Z
    PLoS ONE, 2014;9(4):e93423.
    Species: Human
    Sample Types: Whole Cells
    Applications: Bioassay
  22. The epithelial calcium channel TRPV5 is regulated differentially by klotho and sialidase.
    Authors: Leunissen E, Nair A, Bull C, Lefeber D, van Delft F, Bindels R, Hoenderop J
    J Biol Chem, 2013;288(41):29238-46.
    Species: Human
    Sample Types: Whole Cells
    Applications: Bioassay
  23. Plasma Klotho is not related to kidney function and does not predict adverse outcome in patients with chronic kidney disease.
    Authors: Seiler S, Wen M, Roth H, Fehrenz M, Flugge F, Herath E, Weihrauch A, Fliser D, Heine G
    Kidney Int, 2012;83(1):121-8.
    Species: N/A
    Sample Types: N/A
    Applications: ELISA (Control)

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