Gene: KL - Homo sapiens
Last modified: Dec 09, 2014. Release 1 • Page created: May 19, 2024
Summary
Gene Symbol | : | KL | ||||||||||||||||
NCBI Gene ID | : | 9365 | ||||||||||||||||
Species | : | Homo sapiens | ||||||||||||||||
Gene Synonyms | : | ALPHA-KLOTHO | KL | KLOTHO | klotho Source: GPSDB |
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Gene Homologs | : | KL (Bos taurus) | KL (Canis lupus familiaris) | KL (Gallus gallus) | KL (Homo sapiens) | Kl (Mus musculus) | KL (Pan troglodytes) | Kl (Rattus norvegicus) | LOC562316 (Danio rerio) | LOC714042 (Macaca mulatta) | ||||||||||||||||
Ageing Relevance Analysis | : |
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Ageing Factor Stable ID | : | AF_003100 | ||||||||||||||||
Download | : | XML |
Protein Information
Protein Name | Species | UniProt Accession Number | UniProt Entry Name | Protein Function | Sequence |
---|---|---|---|---|---|
Klotho | Homo sapiens | Q9UEF7 (UniProtKB/Swiss-Prot) | KLOT_HUMAN (UniProtKB/Swiss-Prot) | The Klotho peptide generated by cleavage of the membrane-bound isoform may be an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling. | View |
Observations
Ageing Phenotype
Data Type 1
Ageing Relevance:
- yes (Exp. Analysis)
- yes, but no ageing factor assigned (Exp. Analysis)
- no (Exp. Analysis)
- putative (Comp. Analysis)
# | Observation Stable ID | Species | Gene | Other Ageing Factor | Description | PubMed | Source | ||||
---|---|---|---|---|---|---|---|---|---|---|---|
1 | OB_009662 | Homo sapiens |
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The KL gene encodes two proteins: one membrane protein and one secreted transcript that acts as a circulating hormone. Mice mutant for KL show multiple signs of accelerated ageing [0020]. In contrast, overexpression of KL in mice increases lifespan by 20-30%, perhaps through a repression of intracellular INS/IGF1 signals [1485]. KL alleles have also been implicated in human longevity and age-related diseases [0146]. Even though its exact functions remain a mystery, KL may be involved in calcium metabolism and in a vitamin D endocrine system. Premature ageing phenotypes in mice mutant for KL are largely rescued by keeping the animals on a vitamin-D-deficient diet [0245]. KL might also exert its actions through FGF23 [1851]. It is plausible that KL plays some role in human ageing but more work is necessary to confirm this notion and elucidate the mechanisms involved. | GenAge |
Data Type 2
no ageing phenotype observation—data type 2 available
Homology Analysis
Ageing Relevance:
- yes (Exp. Analysis)
- yes, but no ageing factor assigned (Exp. Analysis)
- no (Exp. Analysis)
- putative (Comp. Analysis)
Legend:
- #EGHG:
- Number of Experimentally Confirmed Ageing-related Genes In Homology Group
# | Observation Stable ID | Homology Group Genes | #EGHG | Description | Source | Homology Source | ||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | OB_008226 |
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2 | The HomoloGene homology group 68415 contains 2 genes with experimental evidence for ageing relevance (KL - Homo sapiens | Kl - Mus musculus) and 7 other genes. | AgeFactDB Homology Analysis | HomoloGene homology group 68415 |
Sequences
KLOT_HUMAN | Q9UEF7 | Klotho (Homo sapiens) from UniProtKB/Swiss-Prot Length: 1012 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 300 310 320 330 340 350 360 370 380 390 400 410 420 430 440 450 460 470 480 490 500 510 520 530 540 550 560 570 580 590 600 610 620 630 640 650 660 670 680 690 700 710 720 730 740 750 760 770 780 790 800 810 820 830 840 850 860 870 880 890 900 910 920 930 940 950 960 970 980 990 1000 1010 KLOT_HUMAN 1 MPASAPPRRPRPPPPSLSLLLVLLGLGGRRLRAEPGDGAQTWARFSRPPAPEAAGLFQGTFPDGFLWAVGSAAYQTEGGWQQHGKGASIWDTFTHHPLAPPGDSRNASLPLGAPSPLQPATGDVASDSYNNVFRDTEALRELGVTHYRFSISWARVLPNGSAGVPNREGLRYYRRLLERLRELGVQPVVTLYHWDLPQRLQDAYGGWANRALADHFRDYAELCFRHFGGQVKYWITIDNPYVVAWHGYATGRLAPGIRGSPRLGYLVAHNLLLAHAKVWHLYNTSFRPTQGGQVSIALSSHWINPRRMTDHSIKECQKSLDFVLGWFAKPVFIDGDYPESMKNNLSSILPDFTESEKKFIKGTADFFALCFGPTLSFQLLDPHMKFRQLESPNLRQLLSWIDLEFNHPQIFIVENGWFVSGTTKRDDAKYMYYLKKFIMETLKAIKLDGVDVIGYTAWSLMDGFEWHRGYSIRRGLFYVDFLSQDKMLLPKSSALFYQKLIEKNGFPPLPENQPLEGTFPCDFAWGVVDNYIQVDTTLSQFTDLNVYLWDVHHSKRLIKVDGVVTKKRKSYCVDFAAIQPQIALLQEMHVTHFRFSLDWALILPLGNQSQVNHTILQYYRCMASELVRVNITPVVALWQPMAPNQGLPRLLARQGAWENPYTALAFAEYARLCFQELGHHVKLWITMNEPYTRNMTYSAGHNLLKAHALAWHVYNEKFRHAQNGKISIALQADWIEPACPFSQKDKEVAERVLEFDIGWLAEPIFGSGDYPWVMRDWLNQRNNFLLPYFTEDEKKLIQGTFDFLALSHYTTILVDSEKEDPIKYNDYLEVQEMTDITWLNSPSQVAVVPWGLRKVLNWLKFKYGDLPMYIISNGIDDGLHAEDDQLRVYYMQNYINEALKAHILDGINLCGYFAYSFNDRTAPRFGLYRYAADQFEPKASMKHYRKIIDSNGFPGPETLERFCPEEFTVCTECSFFHTRKSLLAFIAFLFFASIISLSLIFYYSKKGRRSYK 1012
References
MeSH Terms: Only a subset of the Medical Subject Headings terms is shown: the Major Topics MeSH terms. They describe one of the main topics discussed in the article denoted by an asterisk on the MeSH term or MeSH/Subheading combination on the PubMed page. MeSH terms that belong to the Ageing MeSH are highlighted in green.
- 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:
Mutation of the mouse klotho gene leads to a syndrome resembling ageing.
Nature. 1997; 390: 45-51.
PubMed (ID: 9363890), doi:10.1038/36285
MeSH Terms: Aging/genetics; Membrane Proteins/genetics - Nagai T, Yamada K, Kim HC, Kim YS, Noda Y, Imura A, Nabeshima Y, Nabeshima T:
Cognition impairment in the genetic model of aging klotho gene mutant mice: a role of oxidative stress.
FASEB J. 2003; 17: 50-2.
PubMed (ID: 12475907), doi:10.1096/fj.02-0448fje
MeSH Terms: Aging; Cognition; Membrane Proteins/genetics; Membrane Proteins/physiology; Oxidative Stress - Arking DE, Becker DM, Yanek LR, Fallin D, Judge DP, Moy TF, Becker LC, Dietz HC:
KLOTHO allele status and the risk of early-onset occult coronary artery disease.
Am J Hum Genet. 2003; 72: 1154-61.
PubMed (ID: 12669274), PubMed Central (ID: PMC1180268), doi:10.1086/375035
MeSH Terms: Alleles; Coronary Artery Disease/genetics; Membrane Proteins/genetics - Tsujikawa H, Kurotaki Y, Fujimori T, Fukuda K, Nabeshima Y:
Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system.
Mol Endocrinol. 2003; 17: 2393-403.
PubMed (ID: 14528024), doi:10.1210/me.2003-0048
MeSH Terms: Aging, Premature/genetics; Membrane Proteins/genetics; Vitamin D/physiology - Tohyama O, Imura A, Iwano A, Freund JN, Henrissat B, Fujimori T, Nabeshima Y:
Klotho is a novel beta-glucuronidase capable of hydrolyzing steroid beta-glucuronides.
J Biol Chem. 2004; 279: 9777-84.
PubMed (ID: 14701853), doi:10.1074/jbc.M312392200
MeSH Terms: Cell Membrane/metabolism; Estradiol/analogs & derivatives; Estriol/analogs & derivatives; Membrane Proteins/physiology; Steroids/chemistry - Quarrie JK, Riabowol KT:
Murine models of life span extension.
Sci Aging Knowledge Environ. 2004; 2004: re5.
PubMed (ID: 15295107), doi:10.1126/sageke.2004.31.re5
MeSH Terms: Aging/genetics; Longevity/genetics; Models, Animal - Shimada T, Takeshita Y, Murohara T, Sasaki K, Egami K, Shintani S, Katsuda Y, Ikeda H, Nabeshima Y, Imaizumi T:
Angiogenesis and vasculogenesis are impaired in the precocious-aging klotho mouse.
Circulation. 2004; 110: 1148-55.
PubMed (ID: 15302783), doi:10.1161/01.CIR.0000139854.74847.99
MeSH Terms: Aging, Premature/physiopathology; Collateral Circulation/physiology; Ischemia/physiopathology; Membrane Proteins/deficiency; Neovascularization, Pathologic/etiology - Li SA, Watanabe M, Yamada H, Nagai A, Kinuta M, Takei K:
Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice.
Cell Struct Funct. 2004; 29: 91-9.
PubMed (ID: 15665504)
MeSH Terms: Brain/metabolism; Kidney/metabolism; Membrane Proteins/metabolism; Ovary/metabolism; Testis/metabolism - de Magalhães JP, Cabral JA, Magalhães D:
The influence of genes on the aging process of mice: a statistical assessment of the genetics of aging.
Genetics. 2005; 169: 265-74.
PubMed (ID: 15466429), PubMed Central (ID: PMC1448866), doi:10.1534/genetics.104.032292
MeSH Terms: Aging/physiology; Gene Expression; Genes/physiology; Mortality - Arking DE, Atzmon G, Arking A, Barzilai N, Dietz HC:
Association between a functional variant of the KLOTHO gene and high-density lipoprotein cholesterol, blood pressure, stroke, and longevity.
Circ Res. 2005; 96: 412-8.
PubMed (ID: 15677572), doi:10.1161/01.RES.0000157171.04054.30
MeSH Terms: Blood Pressure/genetics; Cholesterol, HDL/blood; Longevity/genetics; Stroke/genetics - Deary IJ, Harris SE, Fox HC, Hayward C, Wright AF, Starr JM, Whalley LJ:
KLOTHO genotype and cognitive ability in childhood and old age in the same individuals.
Neurosci Lett. 2005; 378: 22-7.
PubMed (ID: 15763166), doi:10.1016/j.neulet.2004.12.005
MeSH Terms: Aging; Cognition/physiology; Intelligence/genetics; Membrane Proteins/genetics - Okada S, Yoshida T, Hong Z, Ishii G, Hatano M, Kuro-O M, Nabeshima Y, Nabeshima Y, Tokuhisa T:
Impairment of B lymphopoiesis in precocious aging (klotho) mice.
Int Immunol. 2000; 12: 861-71.
PubMed (ID: 10837414)
MeSH Terms: Aging/immunology; B-Lymphocytes/physiology; Hematopoiesis - 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:
Suppression of aging in mice by the hormone Klotho.
Science. 2005; 309: 1829-33.
PubMed (ID: 16123266), PubMed Central (ID: PMC2536606), doi:10.1126/science.1112766
MeSH Terms: Aging/physiology; Longevity/physiology; Membrane Proteins/genetics; Membrane Proteins/physiology - Masuda H, Chikuda H, Suga T, Kawaguchi H, Kuro-o M:
Regulation of multiple ageing-like phenotypes by inducible klotho gene expression in klotho mutant mice.
Mech Ageing Dev. 2005; 126: 1274-83.
PubMed (ID: 16144705), doi:10.1016/j.mad.2005.07.007
MeSH Terms: Aging; Membrane Proteins/genetics - Yamamoto M, Clark JD, Pastor JV, Gurnani P, Nandi A, Kurosu H, Miyoshi M, Ogawa Y, Castrillon DH, Rosenblatt KP, Kuro-o M:
Regulation of oxidative stress by the anti-aging hormone klotho.
J Biol Chem. 2005; 280: 38029-34.
PubMed (ID: 16186101), PubMed Central (ID: PMC2515369), doi:10.1074/jbc.M509039200
MeSH Terms: Membrane Proteins/genetics; Membrane Proteins/metabolism; Oxidative Stress - Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt KP, Baum MG, Schiavi S, Hu MC, Moe OW, Kuro-o M:
Regulation of fibroblast growth factor-23 signaling by klotho.
J Biol Chem. 2006; 281: 6120-3.
PubMed (ID: 16436388), PubMed Central (ID: PMC2637204), doi:10.1074/jbc.C500457200
MeSH Terms: Fibroblast Growth Factors/metabolism; Glucuronidase/physiology; Signal Transduction/physiology - Razzaque MS, Sitara D, Taguchi T, St-Arnaud R, Lanske B:
Premature aging-like phenotype in fibroblast growth factor 23 null mice is a vitamin D-mediated process.
FASEB J. 2006; 20: 720-2.
PubMed (ID: 16436465), PubMed Central (ID: PMC2899884), doi:10.1096/fj.05-5432fje
MeSH Terms: Aging, Premature/metabolism; Fibroblast Growth Factors/deficiency; Fibroblast Growth Factors/metabolism; Vitamin D/metabolism - de Oliveira RM:
Klotho RNAi induces premature senescence of human cells via a p53/p21 dependent pathway.
FEBS Lett. 2006; 580: 5753-8.
PubMed (ID: 17014852), doi:10.1016/j.febslet.2006.09.036
MeSH Terms: Cell Aging/physiology; Cyclin-Dependent Kinase Inhibitor p21/metabolism; Glucuronidase/metabolism; RNA Interference; Tumor Suppressor Protein p53/metabolism - Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S, Yamashita T:
Klotho converts canonical FGF receptor into a specific receptor for FGF23.
Nature. 2006; 444: 770-4.
PubMed (ID: 17086194), doi:10.1038/nature05315
MeSH Terms: Fibroblast Growth Factors/metabolism; Glucuronidase/metabolism; Receptors, Fibroblast Growth Factor/metabolism; Signal Transduction - 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:
alpha-Klotho as a regulator of calcium homeostasis.
Science. 2007; 316: 1615-8.
PubMed (ID: 17569864), doi:10.1126/science.1135901
MeSH Terms: Calcium/metabolism; Glucuronidase/physiology; Homeostasis - Liu H, Fergusson MM, Castilho RM, Liu J, Cao L, Chen J, Malide D, Rovira II, Schimel D, Kuo CJ, Gutkind JS, Hwang PM, Finkel T:
Augmented Wnt signaling in a mammalian model of accelerated aging.
Science. 2007; 317: 803-6.
PubMed (ID: 17690294), doi:10.1126/science.1143578
MeSH Terms: Aging/physiology; Cell Aging/physiology; Glucuronidase/metabolism; Signal Transduction; Stem Cells/physiology; Wnt Proteins/metabolism - Medici D, Razzaque MS, Deluca S, Rector TL, Hou B, Kang K, Goetz R, Mohammadi M, Kuro-O M, Olsen BR, Lanske B:
FGF-23-Klotho signaling stimulates proliferation and prevents vitamin D-induced apoptosis.
J Cell Biol. 2008; 182: 459-65.
PubMed (ID: 18678710), PubMed Central (ID: PMC2500132), doi:10.1083/jcb.200803024
MeSH Terms: Apoptosis/drug effects; Fibroblast Growth Factors/metabolism; Glucuronidase/metabolism; Vitamin D/pharmacology - Kawaguchi H, Manabe N, Chikuda H, Nakamura K, Kuroo M:
Cellular and molecular mechanism of low-turnover osteopenia in the klotho-deficient mouse.
Cell Mol Life Sci. 2000; 57: 731-7.
PubMed (ID: 10892339)
MeSH Terms: Bone Diseases, Metabolic/genetics; Bone Diseases, Metabolic/pathology; Membrane Proteins/genetics - Wolf I, Levanon-Cohen S, Bose S, Ligumsky H, Sredni B, Kanety H, Kuro-o M, Karlan B, Kaufman B, Koeffler HP, Rubinek T:
Klotho: a tumor suppressor and a modulator of the IGF-1 and FGF pathways in human breast cancer.
Oncogene. 2008; 27: 7094-105.
PubMed (ID: 18762812), doi:10.1038/onc.2008.292
MeSH Terms: Breast Neoplasms/metabolism; Fibroblast Growth Factors/metabolism; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Glucuronidase/physiology; Insulin-Like Growth Factor I/metabolism - Houlihan LM, Harris SE, Luciano M, Gow AJ, Starr JM, Visscher PM, Deary IJ:
Replication study of candidate genes for cognitive abilities: the Lothian Birth Cohort 1936.
Genes Brain Behav. 2009; 8: 238-47.
PubMed (ID: 19077115), doi:10.1111/j.1601-183X.2008.00470.x
MeSH Terms: Cognition/physiology; Intelligence/genetics - Wang Y, Sun Z:
Klotho gene delivery prevents the progression of spontaneous hypertension and renal damage.
Hypertension. 2009; 54: 810-7.
PubMed (ID: 19635988), PubMed Central (ID: PMC2814175), doi:10.1161/HYPERTENSIONAHA.109.134320
MeSH Terms: Gene Transfer Techniques; Glucuronidase/genetics; Hypertension/prevention & control; Kidney Diseases/prevention & control; Kidney Tubules/pathology - Semba RD, Cappola AR, Sun K, Bandinelli S, Dalal M, Crasto C, Guralnik JM, Ferrucci L:
Plasma klotho and mortality risk in older community-dwelling adults.
J Gerontol A Biol Sci Med Sci. 2011; 66: 794-800.
PubMed (ID: 21474560), PubMed Central (ID: PMC3143348), doi:10.1093/gerona/glr058
MeSH Terms: Aging/blood; Geriatric Assessment/methods; Glucuronidase/blood; Longevity/physiology - Utsugi T, Ohno T, Ohyama Y, Uchiyama T, Saito Y, Matsumura Y, Aizawa H, Itoh H, Kurabayashi M, Kawazu S, Tomono S, Oka Y, Suga T, Kuro-o M, Nabeshima Y, Nagai R:
Decreased insulin production and increased insulin sensitivity in the klotho mutant mouse, a novel animal model for human aging.
Metab Clin Exp. 2000; 49: 1118-23.
PubMed (ID: 11016890), doi:10.1053/meta.2000.8606
MeSH Terms: Aging/physiology; Insulin/blood; Insulin/pharmacology; Models, Biological; Muscle Proteins - Arking DE, Krebsova A, Macek M, Macek M, Arking A, Mian IS, Fried L, Hamosh A, Dey S, McIntosh I, Dietz HC:
Association of human aging with a functional variant of klotho.
Proc Natl Acad Sci USA. 2002; 99: 856-61.
PubMed (ID: 11792841), PubMed Central (ID: PMC117395), doi:10.1073/pnas.022484299
MeSH Terms: Aging/genetics; Membrane Proteins/genetics - Ogata N, Matsumura Y, Shiraki M, Kawano K, Koshizuka Y, Hosoi T, Nakamura K, Kuro-O M, Kawaguchi H:
Association of klotho gene polymorphism with bone density and spondylosis of the lumbar spine in postmenopausal women.
Bone. 2002; 31: 37-42.
PubMed (ID: 12110410)
MeSH Terms: Bone Density/genetics; Membrane Proteins/genetics; Osteoporosis, Postmenopausal/genetics; Polymorphism, Genetic/genetics; Spinal Osteophytosis/genetics - Manya H, Inomata M, Fujimori T, Dohmae N, Sato Y, Takio K, Nabeshima Y, Endo T:
Klotho protein deficiency leads to overactivation of mu-calpain.
J Biol Chem. 2002; 277: 35503-8.
PubMed (ID: 12119304), doi:10.1074/jbc.M206033200
MeSH Terms: Calpain/metabolism; Membrane Proteins/physiology - Nabeshima Y:
Klotho: a fundamental regulator of aging.
Ageing Res Rev. 2002; 1: 627-38.
PubMed (ID: 12362891)
MeSH Terms: Aging/physiology; Membrane Proteins/genetics - Kawano K, Ogata N, Chiano M, Molloy H, Kleyn P, Spector TD, Uchida M, Hosoi T, Suzuki T, Orimo H, Inoue S, Nabeshima Y, Nakamura K, Kuro-o M, Kawaguchi H:
Klotho gene polymorphisms associated with bone density of aged postmenopausal women.
J Bone Miner Res. 2002; 17: 1744-51.
PubMed (ID: 12369777), doi:10.1359/jbmr.2002.17.10.1744
MeSH Terms: Aging/genetics; Asian Continental Ancestry Group/genetics; Bone Density/genetics; European Continental Ancestry Group/genetics; Membrane Proteins/genetics; Polymorphism, Single Nucleotide; Postmenopause/genetics
Sources
Ageing-related Data Sources
- AgeFactDB Homology Analysis
- GenAge
Additional Data Sources
- AgeFactDB Pipeline
- GPSDB
- HomoloGene
- NCBI Taxonomy
- PubMed
- UniProtKB/Swiss-Prot