克洛素

克洛素
识别号
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号染色体[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]
基因本体
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;
细胞组分	• integral component of membrane; • 膜; • 细胞膜; • integral component of plasma membrane; • 细胞外区域; • apical plasma membrane; • 外排体; • 胞内; • 细胞外空间;
生物学过程	• 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; • 代谢; • glycosyl compound metabolic process; • phosphatidylinositol phosphate biosynthetic process; • insulin receptor signaling pathway; • fibroblast growth factor receptor signaling pathway; • phosphatidylinositol-3-phosphate biosynthetic process; • 碳水化合物代谢; • 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
	维基数据

克洛素（Klotho，或译可罗素）是一种由人类KL基因编码而成的酵素[5]。

该基因属于第一型跨膜蛋白，且具有β-葡萄糖醛酸苷酶活性。慢性肾衰竭患者体内的可罗素制造会减少，这也可能是造成慢性肾衰后一连串并发症的原因（如动脉硬化、骨质疏松、以及皮肤松弛等等）。该编码基因的突变也与老化、骨质流失有关[6][7]。过度表现可罗素的小鼠，寿命会较野生型小鼠长[8]。

功能

克洛素为一种跨膜蛋白，会调控生物体对于胰岛素的敏感性，且可能也与老化有关。本蛋白最早由黑尾诚等人于1997年发现[9]，该蛋白命名自希腊神话命运三女神中的克洛托（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，与人类老化有关[10][11]。血浆中的循环克洛素会随年纪逐渐减少[12]。β-克洛素会与FGF受体行程协同受体，可与FGF19、FGF20、FGF23等成纤维细胞生长因子（FGF）结合进行作用[13][14]。

克洛素缺乏的小鼠会出现类似人类早衰的症状，并加速动脉血管硬化的进程，同时也会损伤血管新生和内皮调控血管扩张的能力。推论克洛素可能可以通过内皮源性一氧化氮释放来保护心血管系统。

过度表现克洛素的小鼠，平均寿命会较一般小数多出19%至31%[8]。克洛速基因的某些变异还与长寿和增进认知功能相关[15]。

克洛素的作用机转迄今未明，目前已知可以通过提升TRPV5和降低TRPC6的表达调控细胞的钙平衡[16]。此外，克洛素也会增加内向整流离子信道ROMK的表达[16]。克洛素缺乏的小鼠会会增加维他命D的制造[17][18][19][20]。

参考文献

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.
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.
.
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.
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.
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.

延伸阅读

Shimoyama Y, Taki K, Mitsuda Y, Tsuruta Y, Hamajima N, Niwa T. . American Journal of Nephrology. 2009, 30 (4): 383–8. PMID 19690404. doi:10.1159/000235686.
Choi BH, Kim CG, Lim Y, Lee YH, Shin SY. . Gene. Jan 2010, 450 (1–2): 121–7. PMID 19913601. doi:10.1016/j.gene.2009.11.004.
Fukumoto S. . Clinical Calcium. Apr 2009, 19 (4): 523–8. PMID 19329831.
Nabeshima Y. . Journal of Dermatological Science. Dec 2000,. 24 Suppl 1: S15–21. PMID 11137391. doi:10.1016/S0923-1811(00)00136-5.
Razzaque MS. . American Journal of Physiology. Renal Physiology. Mar 2009, 296 (3): F470–6. PMC 2660189 . PMID 19019915. doi:10.1152/ajprenal.90538.2008.
Menon R, Pearce B, Velez DR, Merialdi M, Williams SM, Fortunato SJ, Thorsen P. . Reproductive Biology and Endocrinology. 2009, 7: 62. PMC 2714850 . PMID 19527514. doi:10.1186/1477-7827-7-62.
Prié D, Ureña Torres P, Friedlander G. . Médecine Sciences. May 2009, 25 (5): 489–95. PMID 19480830. doi:10.1051/medsci/2009255489.
Torres PU, Prié D, Beck L, De Brauwere D, Leroy C, Friedlander G. . Journal of Renal Nutrition. Jan 2009, 19 (1): 50–6. PMID 19121771. doi:10.1053/j.jrn.2008.10.018.
Halaschek-Wiener J, Amirabbasi-Beik M, Monfared N, Pieczyk M, Sailer C, Kollar A, Thomas R, Agalaridis G, Yamada S, Oliveira L, Collins JA, Meneilly G, Marra MA, Madden KM, Le ND, Connors JM, Brooks-Wilson AR. Mary Bridger J , 编. . PLOS ONE. 2009, 4 (8): e6641. Bibcode:2009PLoSO...4.6641H. PMC 2722017 . PMID 19680556. doi:10.1371/journal.pone.0006641.
Shimoyama Y, Nishio K, Hamajima N, Niwa T. . Clinica Chimica Acta; International Journal of Clinical Chemistry. Aug 2009, 406 (1–2): 134–8. PMID 19539617. doi:10.1016/j.cca.2009.06.011.
Wang HL, Xu Q, Wang Z, Zhang YH, Si LY, Li XJ, Yang QH, Xiao H. . Clinica Chimica Acta; International Journal of Clinical Chemistry. Mar 2010, 411 (5–6): 386–90. PMID 20005218. doi:10.1016/j.cca.2009.12.004.
Yerges LM, Klei L, Cauley JA, Roeder K, Kammerer CM, Moffett SP, Ensrud KE, Nestlerode CS, Marshall LM, Hoffman AR, Lewis C, Lang TF, Barrett-Connor E, Ferrell RE, Orwoll ES, Zmuda JM. . Journal of Bone and Mineral Research. Dec 2009, 24 (12): 2039–49. PMC 2791518 . PMID 19453261. doi:10.1359/jbmr.090524.
Torres PU, Prié D, Molina-Blétry V, Beck L, Silve C, Friedlander G. . Kidney International. Apr 2007, 71 (8): 730–7. PMID 17332731. doi:10.1038/sj.ki.5002163.
Kurosu H, Kuro-o M. . Current Opinion in Nephrology and Hypertension. Jul 2008, 17 (4): 368–72. PMID 18660672. doi:10.1097/MNH.0b013e3282ffd994.
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.
Invidia L, Salvioli S, Altilia S, Pierini M, Panourgia MP, Monti D, De Rango F, Passarino G, Franceschi C. . Biogerontology. Feb 2010, 11 (1): 67–73. PMID 19421891. doi:10.1007/s10522-009-9229-z.
Nabeshima Y. . Clinical Calcium. Jul 2008, 18 (7): 923–34. PMID 18591743.
Chen SN, Cilingiroglu M, Todd J, Lombardi R, Willerson JT, Gotto AM, Ballantyne CM, Marian AJ. . BMC Medical Genetics. 2009, 10: 111. PMC 2775733 . PMID 19878569. doi:10.1186/1471-2350-10-111.
Zhang R, Zheng F. . Kidney International. Sep 2008, 74 (6): 702–4. PMID 18756295. doi:10.1038/ki.2008.382.

外部链接

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数据，这些数据属于公共领域。

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[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.