克洛素

克洛素
識別號
别名	KL；, entrez:9365, klotho, HFTC3, KLA
外部ID	OMIM：604824 MGI：1101771 HomoloGene：68415 GeneCards：KL
基因位置（人类）
染色体	13號染色體[1]
终止	33,066,143 bp[1]
基因位置（小鼠）
染色体	小鼠5号染色体[2]
终止	150,917,282 bp[2]
基因本體
分子功能	• hydrolase activity, hydrolyzing O-glycosyl compounds; • hormone activity; • beta-glucuronidase activity; • signal transducer activity; • hydrolase activity, acting on glycosyl bonds; • vitamin D binding; • fibroblast growth factor binding; • beta-glucosidase activity; • 水解酶活性; • phosphatidylinositol-4,5-bisphosphate 3-kinase activity; • fibroblast growth factor receptor binding; • 1-phosphatidylinositol-3-kinase activity;
細胞組分	• integral component of membrane; • 膜; • 细胞膜; • integral component of plasma membrane; • 細胞外區域; • apical plasma membrane; • 外排體; • 胞內; • 細胞外空間;
生物學過程	• calcium ion homeostasis; • positive regulation of bone mineralization; • 老化; • MAPK cascade; • positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway; • energy reserve metabolic process; • 代謝; • glycosyl compound metabolic process; • phosphatidylinositol phosphate biosynthetic process; • insulin receptor signaling pathway; • fibroblast growth factor receptor signaling pathway; • phosphatidylinositol-3-phosphate biosynthetic process; • 碳水化合物代謝; • regulation of signaling receptor activity; • positive regulation of protein kinase B signaling; • regulation of molecular function;
	Sources:Amigo / QuickGO
直系同源
	9365
	16591
	ENSG00000133116
	ENSMUSG00000058488
	Q9UEF7
	O35082
	NM_004795; NM_153683
	NM_013823
	NP_004786
	NP_038851
	維基數據

克洛素（Klotho，或譯可羅素）是一種由人類KL基因編碼而成的酵素[5]。

該基因屬於第一型跨膜蛋白，且具有β-葡萄糖醛酸苷酶活性。慢性腎衰竭患者體內的可羅素製造會減少，這也可能是造成慢性腎衰後一連串併發症的原因（如動脈硬化、骨質疏鬆、以及皮膚鬆弛等等）。該編碼基因的突變也與老化、骨質流失有關[6][7]。過度表現可羅素的小鼠，壽命會較野生型小鼠長[8]。

功能

克洛素為一種跨膜蛋白，會調控生物體對於胰島素的敏感性，且可能也與老化有關。本蛋白最早由黑尾誠等人於1997年發現[9]，該蛋白命名自希腊神话命運三女神中的克洛托（Klotho）。

克洛素具有β-葡萄糖醛酸苷酶活性，可以水解β-葡萄糖醛酸，與人類老化有關[10][11]。血漿中的循環克洛素會隨年紀逐漸減少[12]。β-克洛素會與FGF受體行程協同受體，可與FGF19、FGF20、FGF23等成纤维细胞生长因子（FGF）結合進行作用[13][14]。

克洛素缺乏的小鼠會出現類似人類早衰的症狀，並加速动脉血管硬化的進程，同時也會損傷血管新生和內皮調控血管擴張的能力。推論克洛素可能可以透過內皮源性一氧化氮釋放來保護心血管系統。

過度表現克洛素的小鼠，平均壽命會較一般小數多出19%至31%[8]。克洛速基因的某些變異還與長壽和增進認知功能相關[15]。

克洛素的作用機轉迄今未明，目前已知可以透過提升TRPV5和降低TRPC6的表達調控細胞的鈣平衡[16]。此外，克洛素也會增加內向整流離子通道ROMK的表達[16]。克洛素缺乏的小鼠會會增加維他命D的製造[17][18][19][20]。

參考文獻

GRCh38: Ensembl release 89: ENSG00000133116 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000058488 - Ensembl, May 2017
. National Center for Biotechnology Information, U.S. National Library of Medicine.
. National Center for Biotechnology Information, U.S. National Library of Medicine.
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.
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Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI. . Nature. Nov 1997, 390 (6655): 45–51. Bibcode:1997Natur.390...45K. PMID 9363890. doi:10.1038/36285.
Arking DE, Krebsova A, Macek M, Macek M, Arking A, Mian IS, Fried L, Hamosh A, Dey S, McIntosh I, Dietz HC. . Proceedings of the National Academy of Sciences of the United States of America. Jan 2002, 99 (2): 856–61. Bibcode:2002PNAS...99..856A. PMC 117395 . PMID 11792841. doi:10.1073/pnas.022484299.
Rodriguez T. . Journal of Molecular Biology Research. 2015, 5 (1): 11. doi:10.5539/jmbr.v5n1p11.
Xiao NM, Zhang YM, Zheng Q, Gu J. . Chinese Medical Journal. May 2004, 117 (5): 742–7. PMID 15161545.
Helsten T, Schwaederle M, Kurzrock R. . Cancer Metastasis Reviews. 2015, 34 (3): 479–96. PMC 4573649 . PMID 26224133. doi:10.1007/s10555-015-9579-8.
Talukdar S, Owen BM, Song P, Hernandez G, Zhang Y, Zhou Y, Scott WT, Paratala B, Turner T, Smith A, Bernardo B, Müller CP, Tang H, Mangelsdorf DJ, Goodwin B, Kliewer SA. . Cell Metabolism. February 2016, 23 (2): 344–9. PMC 4749404 . PMID 26724861. doi:10.1016/j.cmet.2015.12.008.
Dena B. Dubal et al., Life Extension Factor Klotho Enhances Cognition, Cell Reports, 2014, DOI: 10.1016/j.celrep.2014.03.076 (open access)
Huang CL. . Kidney International. May 2010, 77 (10): 855–60. PMID 20375979. doi:10.1038/ki.2010.73.
Kuro-o M. . Biochimica et Biophysica Acta. Oct 2009, 1790 (10): 1049–58. PMC 2743784 . PMID 19230844. doi:10.1016/j.bbagen.2009.02.005.
Medici D, Razzaque MS, Deluca S, Rector TL, Hou B, Kang K, Goetz R, Mohammadi M, Kuro-O M, Olsen BR, Lanske B. . The Journal of Cell Biology. Aug 2008, 182 (3): 459–65. PMC 2500132 . PMID 18678710. doi:10.1083/jcb.200803024.
Tsujikawa H, Kurotaki Y, Fujimori T, Fukuda K, Nabeshima Y. . Molecular Endocrinology. Dec 2003, 17 (12): 2393–403. PMID 14528024. doi:10.1210/me.2003-0048.
Imura A, Tsuji Y, Murata M, Maeda R, Kubota K, Iwano A, Obuse C, Togashi K, Tominaga M, Kita N, Tomiyama K, Iijima J, Nabeshima Y, Fujioka M, Asato R, Tanaka S, Kojima K, Ito J, Nozaki K, Hashimoto N, Ito T, Nishio T, Uchiyama T, Fujimori T, Nabeshima Y. . Science. Jun 2007, 316 (5831): 1615–8. Bibcode:2007Sci...316.1615I. PMID 17569864. doi:10.1126/science.1135901.

延伸閱讀

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Kuro-o M. . Biochimica et Biophysica Acta. Oct 2009, 1790 (10): 1049–58. PMC 2743784 . PMID 19230844. doi:10.1016/j.bbagen.2009.02.005.
Wolf I, Laitman Y, Rubinek T, Abramovitz L, Novikov I, Beeri R, Kuro-O M, Koeffler HP, Catane R, Freedman LS, Levy-Lahad E, Karlan BY, Friedman E, Kaufman B. . Oncogene. Jan 2010, 29 (1): 26–33. PMID 19802015. doi:10.1038/onc.2009.301.
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外部連結

Entrez Gene entry for Klotho
GenAge entry for Klotho （页面存档备份，存于）

克洛素引用了美国国家医学图书馆提供的資料，这些資料属于公共领域。

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000133116 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000058488 - Ensembl, May 2017

[3] . National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] . National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9464267-5] Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M, Nabeshima Y. . Biochemical and Biophysical Research Communications. Jan 1998, 242 (3): 626–30. PMID 9464267. doi:10.1006/bbrc.1997.8019.

[entrez-6] .

[SchumannLiu2016-7] Schumann G, Liu C, O'Reilly P, Gao H, Song P, Xu B, et al. . Proceedings of the National Academy of Sciences of the United States of America. 2016, 113 (50): 14372–14377. PMC 5167198 . PMID 27911795. doi:10.1073/pnas.1611243113.

[pmid16123266-8] Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H, Shimomura I, Takayama Y, Herz J, Kahn CR, Rosenblatt KP, Kuro-o M. . Science. Sep 2005, 309 (5742): 1829–33. Bibcode:2005Sci...309.1829K. PMC 2536606 . PMID 16123266. doi:10.1126/science.1112766.

[pmid9363890-9] Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI. . Nature. Nov 1997, 390 (6655): 45–51. Bibcode:1997Natur.390...45K. PMID 9363890. doi:10.1038/36285.

[pmid11792841-10] Arking DE, Krebsova A, Macek M, Macek M, Arking A, Mian IS, Fried L, Hamosh A, Dey S, McIntosh I, Dietz HC. . Proceedings of the National Academy of Sciences of the United States of America. Jan 2002, 99 (2): 856–61. Bibcode:2002PNAS...99..856A. PMC 117395 . PMID 11792841. doi:10.1073/pnas.022484299.

[11] Rodriguez T. . Journal of Molecular Biology Research. 2015, 5 (1): 11. doi:10.5539/jmbr.v5n1p11.

[pmid15161545-12] Xiao NM, Zhang YM, Zheng Q, Gu J. . Chinese Medical Journal. May 2004, 117 (5): 742–7. PMID 15161545.

[pmid26224133-13] Helsten T, Schwaederle M, Kurzrock R. . Cancer Metastasis Reviews. 2015, 34 (3): 479–96. PMC 4573649 . PMID 26224133. doi:10.1007/s10555-015-9579-8.

[FGF21_receptor_expression_in_the_brain-14] Talukdar S, Owen BM, Song P, Hernandez G, Zhang Y, Zhou Y, Scott WT, Paratala B, Turner T, Smith A, Bernardo B, Müller CP, Tang H, Mangelsdorf DJ, Goodwin B, Kliewer SA. . Cell Metabolism. February 2016, 23 (2): 344–9. PMC 4749404 . PMID 26724861. doi:10.1016/j.cmet.2015.12.008.

[15] Dena B. Dubal et al., Life Extension Factor Klotho Enhances Cognition, Cell Reports, 2014, DOI: 10.1016/j.celrep.2014.03.076 (open access)

[Huang_et_al_2010-16] Huang CL. . Kidney International. May 2010, 77 (10): 855–60. PMID 20375979. doi:10.1038/ki.2010.73.

[17] Kuro-o M. . Biochimica et Biophysica Acta. Oct 2009, 1790 (10): 1049–58. PMC 2743784 . PMID 19230844. doi:10.1016/j.bbagen.2009.02.005.

[18] Medici D, Razzaque MS, Deluca S, Rector TL, Hou B, Kang K, Goetz R, Mohammadi M, Kuro-O M, Olsen BR, Lanske B. . The Journal of Cell Biology. Aug 2008, 182 (3): 459–65. PMC 2500132 . PMID 18678710. doi:10.1083/jcb.200803024.

[pmid14528024-19] Tsujikawa H, Kurotaki Y, Fujimori T, Fukuda K, Nabeshima Y. . Molecular Endocrinology. Dec 2003, 17 (12): 2393–403. PMID 14528024. doi:10.1210/me.2003-0048.

[pmid17569864-20] Imura A, Tsuji Y, Murata M, Maeda R, Kubota K, Iwano A, Obuse C, Togashi K, Tominaga M, Kita N, Tomiyama K, Iijima J, Nabeshima Y, Fujioka M, Asato R, Tanaka S, Kojima K, Ito J, Nozaki K, Hashimoto N, Ito T, Nishio T, Uchiyama T, Fujimori T, Nabeshima Y. . Science. Jun 2007, 316 (5831): 1615–8. Bibcode:2007Sci...316.1615I. PMID 17569864. doi:10.1126/science.1135901.