Recombinant Mouse Klotho (aa 35-982) Protein, CF

• Reactivity: Mu
• Applications: Bioactivity
• Format: Carrier-Free

Recombinant Mouse Klotho (aa 35-982) Protein, CF Summary

• Details of Functionality: Measured in a cell proliferation assay using BaF3 mouse pro-B cells transfected with human FGF RIIIc. The ED 50 for this effect is 0.04-0.4 µg/mL in the presence of 1 µg/mL of Recombinant Human FGF-23 (Catalog # 2604-FG) and 10 µg/mL of heparin.
• Source: Chinese Hamster Ovary cell line, CHO-derived mouse Klotho protein Ala35-Lys982, with a C-terminal 6-His tag
• Accession #: O35082.2
• N-terminal Sequence: Ala35
• Protein/Peptide Type: Recombinant Proteins
• Gene: Kl
• Purity: >90%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.
• Endotoxin Note: <0.01 EU per 1 μg of the protein by the LAL method.

Applications/Dilutions

• Dilutions:
  • Bioactivity
• Theoretical MW: 109.5 kDa.
  Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors.
• SDS-PAGE: 125-130 kDa, reducing conditions

Packaging, Storage & Formulations

• Storage: Use a manual defrost freezer and avoid repeated freeze-thaw cycles.
  12 months from date of receipt, -70 degreesC as supplied. 1 month, 2 to 8 degreesC under sterile conditions after opening.
• Buffer: Supplied as a 0.2 μm filtered solution in PBS, Glycerol and EDTA.
• Purity: >90%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.

Notes

This product is produced by and ships from R&D Systems, Inc., a Bio-Techne brand.

Alternate Names for Recombinant Mouse Klotho (aa 35-982) Protein, CF

• EC 3.2.1
• EC 3.2.1.31
• KL
• Klotho

Background

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 1014 amino acid (aa) type I transmembrane protein contains a 34 aa signal sequence, a 948 aa extracellular domain (ECD) containing two extracellular glycosidase-like domains, a 21 aa transmembrane domain and an 11 aa intracellular domain. Within the ECD, mouse Klotho shares 95%, 87% and 87% aa identity with rat, human and equine Klotho, respectively. Although a truncated 554 aa isoform predicts a soluble 70 kDa form, the soluble form found in plasma and cerebrospinal fluid is a 130 kDa form produced by proteolytic cleavage of the glycosylated 135 kDa full-length Klotho (3, 4). A prominent intracellular 120 kDa form of Klotho is localized to endoplasmic reticulum and Golgi membranes (4). Klotho is named for the Greek goddess who spins the thread of life. 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 FGF23 with FGF R1 (6). This interaction negatively regulates 1 alpha -hydroxylase, the rate-limiting enzyme in the synthesis of 1,25(OH) 2 D 3 (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).

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.

Publications for Klotho (1819-KL)(26)

Publications using 1819-KL

• The, E;Zhai, Y;Yao, Q;Ao, L;Fullerton, DA;Meng, X; Molecular Interaction of Soluble Klotho with FGF23 in the Pathobiology of Aortic Valve Lesions Induced by Chronic Kidney Disease International journal of biological sciences 2024-06-17 [PMID: 38993571] (In vivo assay, Mouse, Transgenic Mouse)
• Orellana, AM;Mazucanti, CH;Dos Anjos, LP;de Sá Lima, L;Kawamoto, EM;Scavone, C; Klotho increases antioxidant defenses in astrocytes and ubiquitin-proteasome activity in neurons Scientific reports 2023-09-12 [PMID: 37699938] (Bioassay, Mouse)
• VW Nakao, CHY Mazucanti, L de Sá Lima, PS de Mello, NM de Souza P, PF Kinoshita, JA Leite, EM Kawamoto, C Scavone Neuroprotective action of alpha-Klotho against LPS-activated glia conditioned medium in primary neuronal culture Scientific Reports, 2022-11-07;12(1):18884. 2022-11-07 [PMID: 36344527] (Bioassay, Mouse)
• S Shrestha, E Adib, J Imani, DJ Aguiar, AM Lamattina, DD Tassew, EP Henske, MA Perrella, C Priolo, S El-Chemaly Angiotensin II receptor type 1 blockade regulates Klotho expression to induce TSC2-deficient cell death The Journal of Biological Chemistry, 2022-10-08;0(0):102580. 2022-10-08 [PMID: 36220392] (Cell Culture, Rat)
• Y Wu, W Liao, J Chen, C Liu, S Zhang, K Yu, X Wang, M Chen, S Wang, X Ran, Y Su, T Cheng, J Wang, C Du Phosphate Metabolic Inhibition Contributes to Irradiation-Induced Myelosuppression through Dampening Hematopoietic Stem Cell Survival Nutrients, 2022-08-18;14(16):. 2022-08-18 [PMID: 36014901] (In Vivo, Mouse)
• 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 Renal Klotho and inorganic phosphate are extrinsic factors that antagonistically regulate hematopoietic stem cell maintenance Cell Reports, 2022-02-15;38(7):110392. 2022-02-15 [PMID: 35172146] (Bioassay, Mouse)
• X Zhuang, X Sun, H Zhou, S Zhang, X Zhong, X Xu, Y Guo, Z Xiong, M Liu, Y Lin, M Zhang, X Liao Klotho attenuated Doxorubicin-induced cardiomyopathy by alleviating Dynamin-related protein 1 - mediated mitochondrial dysfunction Mechanisms of Ageing and Development, 2021-02-01;195(0):111442. 2021-02-01 [PMID: 33539906] (Bioassay, Mouse)
• T Landry, P Li, D Shookster, Z Jiang, H Li, BT Laing, W Bunner, T Langton, Q Tong, H Huang Centrally circulating &amp;alpha-klotho inversely correlates with human obesity and modulates arcuate cell populations in mice Molecular Metabolism, 2020-12-07;44(0):101136. 2020-12-07 [PMID: 33301986] (In Vivo, Mouse)
• 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 Soluble Klotho, a biomarker and therapeutic strategy to reduce bronchopulmonary dysplasia and pulmonary hypertension in preterm infants Sci Rep, 2020-07-23;10(1):12368. 2020-07-23 [PMID: 32704023] (In Vivo, Rat)
• Z Zhang, Q Nian, G Chen, S Cui, Y Han, J Zhang Klotho Alleviates Lung Injury Caused by Paraquat via Suppressing ROS/P38 MAPK-Regulated Inflammatory Responses and Apoptosis Oxid Med Cell Longev, 2020-05-13;2020(0):1854206. 2020-05-13 [PMID: 32509139] (In Vivo, Mouse)
• WY Chen Soluble Alpha-Klotho Alleviates Cardiac Fibrosis without Altering Cardiomyocytes Renewal Int J Mol Sci, 2020-03-22;21(6):. 2020-03-22 [PMID: 32235720] (Bioassay, Rat)
• Z Rao, T Landry, P Li, W Bunner, BT Laing, Y Yuan, H Huang Administration of alpha klotho reduces liver and adipose lipid accumulation in obese mice Heliyon, 2019-04-24;5(4):e01494. 2019-04-24 [PMID: 31049427] (In Vivo, Mouse)
• L Zhu, LR Stein, D Kim, K Ho, GQ Yu, L Zhan, TE Larsson, L Mucke Klotho controls the brain-immune system interface in the choroid plexus Proc. Natl. Acad. Sci. U.S.A., 2018-11-09;0(0):. 2018-11-09 [PMID: 30413620] (Bioassay, Mouse)
• 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 Klotho suppresses colorectal cancer through modulation of the unfolded protein response Oncogene, 2018-09-19;0(0):. 2018-09-19 [PMID: 30232408] (In Vivo, Mouse)
• T Minamizaki, Y Konishi, K Sakurai, H Yoshioka, JE Aubin, K Kozai, Y Yoshiko Soluble Klotho causes hypomineralization in Klotho-deficient mice J. Endocrinol., 2018-04-09;0(0):. 2018-04-09 [PMID: 29632215] (In Vivo, Mouse)
• Y Qian, X Guo, L Che, X Guan, B Wu, R Lu, M Zhu, H Pang, Y Yan, Z Ni, L Gu Klotho Reduces Necroptosis by Targeting Oxidative Stress Involved in Renal Ischemic-Reperfusion Injury Cell. Physiol. Biochem., 2018-03-10;45(6):2268-2282. 2018-03-10 [PMID: 29550818] (In Vivo, Mouse)
• CH Mazucanti, EM Kawamoto, MP Mattson, C Scavone, S Camandola Activity-dependent neuronal Klotho enhances astrocytic aerobic glycolysis J. Cereb. Blood Flow Metab., 2018-03-01;0(0):271678X187627. 2018-03-01 [PMID: 29493420] (Bioassay, Mouse)
• F Salech, L Varela-Nal, SB Arredondo, DB Bustamante, GA Andaur, R Cisneros, DP Ponce, P Ayala, NC Inestrosa, JL Valdés, MI Behrens, A Couve Local Klotho enhances neuronal progenitor proliferation in the adult hippocampus J. Gerontol. A Biol. Sci. Med. Sci., 2019-06-18;0(0):. 2019-06-18 [PMID: 29300914] (Bioassay, Mouse)
• J Leon, AJ Moreno, BI Garay, RJ Chalkley, AL Burlingame, D Wang, DB Dubal Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and ?-Synuclein Transgenic Mice Cell Rep, 2017-08-08;20(6):1360-1371. 2017-08-08 [PMID: 28793260] (In Vivo, Mouse)
• SW Lim, L Jin, K Luo, J Jin, YJ Shin, SY Hong, CW Yang Klotho enhances FoxO3-mediated manganese superoxide dismutase expression by negatively regulating PI3K/AKT pathway during tacrolimus-induced oxidative stress Cell Death Dis, 2017-08-03;8(8):e2972. 2017-08-03 [PMID: 28771227] (In Vivo, Mouse)
• 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 Inhibition of age-related therapy resistance in melanoma by rosiglitazone-mediated induction of Klotho Clin. Cancer Res, 2017-02-23;0(0):. 2017-02-23 [PMID: 28232477] (In Vivo, Mouse)
• Andrukhova O, Smorodchenko A, Egerbacher M, Streicher C, Zeitz U, Goetz R, Shalhoub V, Mohammadi M, Pohl E, Lanske B, Erben R FGF23 promotes renal calcium reabsorption through the TRPV5 channel. EMBO J, 2014-01-16;33(3):229-46. 2014-01-16 [PMID: 24434184] (Bioassay, Canine)
• Vadakke Madathil S, Coe L, Casu C, Sitara D Klotho deficiency disrupts hematopoietic stem cell development and erythropoiesis. Am J Pathol, 2014-01-08;184(3):827-41. 2014-01-08 [PMID: 24412515] (In Vivo, Mouse)
• Song , Shuang, Gao , Pan, Xiao , Hang, Xu , Yan, Si , Liang Yi Klotho suppresses cardiomyocyte apoptosis in mice with stress-induced cardiac injury via downregulation of endoplasmic reticulum stress. PLoS ONE, 2013-12-10;8(12):e82968. 2013-12-10 [PMID: 24340070] (In Vivo, Mouse)
• Kawai M, Kinoshita S, Kimoto A, Hasegawa Y, Miyagawa K, Yamazaki M, Ohata Y, Ozono K, Michigami T FGF23 suppresses chondrocyte proliferation in the presence of soluble alpha-Klotho both in vitro and in vivo. J Biol Chem, 2012-12-12;288(4):2414-27. 2012-12-12 [PMID: 23235154] (Bioassay, Mouse)
• Lau , Wei Ling, Leaf , Elizabet, Hu , Ming Cha, Takeno , Marc M, Kuro-o , Makoto, Moe , Orson W, Giachelli , Cecilia Vitamin D receptor agonists increase klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet. Kidney Int, 2012-08-29;82(12):1261-70. 2012-08-29 [PMID: 22932118] (Bioassay, Mouse)

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Bioinformatics

• Gene Symbol: Kl
• Uniprot:
  • O35082.2()