Klotho

NameKlotho
Synonyms3.2.1.31
Gene NameKL
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009325|Klotho
MPASAPPRRPRPPPPSLSLLLVLLGLGGRRLRAEPGDGAQTWARFSRPPAPEAAGLFQGT
FPDGFLWAVGSAAYQTEGGWQQHGKGASIWDTFTHHPLAPPGDSRNASLPLGAPSPLQPA
TGDVASDSYNNVFRDTEALRELGVTHYRFSISWARVLPNGSAGVPNREGLRYYRRLLERL
RELGVQPVVTLYHWDLPQRLQDAYGGWANRALADHFRDYAELCFRHFGGQVKYWITIDNP
YVVAWHGYATGRLAPGIRGSPRLGYLVAHNLLLAHAKVWHLYNTSFRPTQGGQVSIALSS
HWINPRRMTDHSIKECQKSLDFVLGWFAKPVFIDGDYPESMKNNLSSILPDFTESEKKFI
KGTADFFALCFGPTLSFQLLDPHMKFRQLESPNLRQLLSWIDLEFNHPQIFIVENGWFVS
GTTKRDDAKYMYYLKKFIMETLKAIKLDGVDVIGYTAWSLMDGFEWHRGYSIRRGLFYVD
FLSQDKMLLPKSSALFYQKLIEKNGFPPLPENQPLEGTFPCDFAWGVVDNYIQVDTTLSQ
FTDLNVYLWDVHHSKRLIKVDGVVTKKRKSYCVDFAAIQPQIALLQEMHVTHFRFSLDWA
LILPLGNQSQVNHTILQYYRCMASELVRVNITPVVALWQPMAPNQGLPRLLARQGAWENP
YTALAFAEYARLCFQELGHHVKLWITMNEPYTRNMTYSAGHNLLKAHALAWHVYNEKFRH
AQNGKISIALQADWIEPACPFSQKDKEVAERVLEFDIGWLAEPIFGSGDYPWVMRDWLNQ
RNNFLLPYFTEDEKKLIQGTFDFLALSHYTTILVDSEKEDPIKYNDYLEVQEMTDITWLN
SPSQVAVVPWGLRKVLNWLKFKYGDLPMYIISNGIDDGLHAEDDQLRVYYMQNYINEALK
AHILDGINLCGYFAYSFNDRTAPRFGLYRYAADQFEPKASMKHYRKIIDSNGFPGPETLE
RFCPEEFTVCTECSFFHTRKSLLAFIAFLFFASIISLSLIFYYSKKGRRSYK
Number of residues1012
Molecular Weight116179.815
Theoretical pINone
GO Classification
Functions
    beta-glucosidase activity
signal transducer activity
fibroblast growth factor binding
beta-glucuronidase activity
vitamin D binding
Processes
    neurotrophin TRK receptor signaling pathway
carbohydrate metabolic process
Ras protein signal transduction
positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway
axon guidance
vascular endothelial growth factor receptor signaling pathway
epidermal growth factor receptor signaling pathway
energy reserve metabolic process
innate immune response
phosphatidylinositol-mediated signaling
Fc-epsilon receptor signaling pathway
acute inflammatory response
activation of MAPKK activity
positive regulation of bone mineralization
calcium ion homeostasis
fibroblast growth factor receptor signaling pathway
aging
small GTPase mediated signal transduction
insulin receptor signaling pathway
MAPK cascade
Components
    extracellular exosome
intracellular
extracellular region
integral component of plasma membrane
plasma membrane
extracellular space
integral component of membrane
General FunctionVitamin d binding
Specific FunctionMay have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in vivo. May be involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D (By similarity). Essential factor for the specific interaction between FGF23 and FGFR1 (By similarity).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.
Transmembrane Regions982-1002
GenBank Protein ID
UniProtKB IDQ9UEF7
UniProtKB Entry NameKLOT_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0017791|Klotho (KL)
ATGCCCGCCAGCGCCCCGCCGCGCCGCCCGCGGCCGCCGCCGCCGTCGCTGTCGCTGCTG
CTGGTGCTGCTGGGCCTGGGCGGCCGCCGCCTGCGTGCGGAGCCGGGCGACGGCGCGCAG
ACCTGGGCCCGTTTCTCGCGGCCTCCTGCCCCCGAGGCCGCGGGCCTCTTCCAGGGCACC
TTCCCCGACGGCTTCCTCTGGGCCGTGGGCAGCGCCGCCTACCAGACCGAGGGCGGCTGG
CAGCAGCACGGCAAGGGTGCGTCCATCTGGGATACGTTCACCCACCACCCCCTGGCACCC
CCGGGAGACTCCCGGAACGCCAGTCTGCCGTTGGGCGCCCCGTCGCCGCTGCAGCCCGCC
ACCGGGGACGTAGCCAGCGACAGCTACAACAACGTCTTCCGCGACACGGAGGCGCTGCGC
GAGCTCGGGGTCACTCACTACCGCTTCTCCATCTCGTGGGCGCGAGTGCTCCCCAATGGC
AGCGCGGGCGTCCCCAACCGCGAGGGGCTGCGCTACTACCGGCGCCTGCTGGAGCGGCTG
CGGGAGCTGGGCGTGCAGCCCGTGGTCACCCTGTACCACTGGGACCTGCCCCAGCGCCTG
CAGGACGCCTACGGCGGCTGGGCCAACCGCGCCCTGGCCGACCACTTCAGGGATTACGCG
GAGCTCTGCTTCCGCCACTTCGGCGGTCAGGTCAAGTACTGGATCACCATCGACAACCCC
TACGTGGTGGCCTGGCACGGCTACGCCACCGGGCGCCTGGCCCCCGGCATCCGGGGCAGC
CCGCGGCTCGGGTACCTGGTGGCGCACAACCTCCTCCTGGCTCATGCCAAAGTCTGGCAT
CTCTACAATACTTCTTTCCGTCCCACTCAGGGAGGTCAGGTGTCCATTGCCCTAAGCTCT
CACTGGATCAATCCTCGAAGAATGACCGACCACAGCATCAAAGAATGTCAAAAATCTCTG
GACTTTGTACTAGGTTGGTTTGCCAAACCCGTATTTATTGATGGTGACTATCCCGAGAGC
ATGAAGAATAACCTTTCATCTATTCTGCCTGATTTTACTGAATCTGAGAAAAAGTTCATC
AAAGGAACTGCTGACTTTTTTGCTCTTTGCTTTGGACCCACCTTGAGTTTTCAACTTTTG
GACCCTCACATGAAGTTCCGCCAATTGGAATCTCCCAACCTGAGGCAACTGCTTTCCTGG
ATTGACCTTGAATTTAACCATCCTCAAATATTTATTGTGGAAAATGGCTGGTTTGTCTCA
GGGACCACCAAGAGAGATGATGCCAAATATATGTATTACCTCAAAAAGTTCATCATGGAA
ACCTTAAAAGCCATCAAGCTGGATGGGGTGGATGTCATCGGGTATACCGCATGGTCCCTC
ATGGATGGTTTCGAGTGGCACAGAGGTTACAGCATCAGGCGTGGACTCTTCTATGTTGAC
TTTCTAAGCCAGGACAAGATGTTGTTGCCAAAGTCTTCAGCCTTGTTCTACCAAAAGCTG
ATAGAGAAAAATGGCTTCCCTCCTTTACCTGAAAATCAGCCCCTAGAAGGGACATTTCCC
TGTGACTTTGCTTGGGGAGTTGTTGACAACTACATTCAAGTAGATACCACTCTGTCTCAG
TTTACCGACCTGAATGTTTACCTGTGGGATGTCCACCACAGTAAAAGGCTTATTAAAGTG
GATGGGGTTGTGACCAAGAAGAGGAAATCCTACTGTGTTGACTTTGCTGCCATCCAGCCC
CAGATCGCTTTACTCCAGGAAATGCACGTTACACATTTTCGCTTCTCCCTGGACTGGGCC
CTGATTCTCCCTCTGGGTAACCAGTCCCAGGTGAACCACACCATCCTGCAGTACTATCGC
TGCATGGCCAGCGAGCTTGTCCGTGTCAACATCACCCCAGTGGTGGCCCTGTGGCAGCCT
ATGGCCCCGAACCAAGGACTGCCGCGCCTCCTGGCCAGGCAGGGCGCCTGGGAGAACCCC
TACACTGCCCTGGCCTTTGCAGAGTATGCCCGACTGTGCTTTCAAGAGCTCGGCCATCAC
GTCAAGCTTTGGATAACGATGAATGAGCCGTATACAAGGAATATGACATACAGTGCTGGC
CACAACCTTCTGAAGGCCCATGCCCTGGCTTGGCATGTGTACAATGAAAAGTTTAGGCAT
GCTCAGAATGGGAAAATATCCATAGCCTTGCAGGCTGATTGGATAGAACCTGCCTGCCCT
TTCTCCCAAAAGGACAAAGAGGTGGCTGAGAGAGTTTTGGAATTTGACATTGGCTGGCTG
GCTGAGCCCATTTTCGGCTCTGGAGATTATCCATGGGTGATGAGGGACTGGCTGAACCAA
AGAAACAATTTTCTTCTTCCTTATTTCACTGAAGATGAAAAAAAGCTAATCCAGGGTACC
TTTGACTTTTTGGCTTTAAGCCATTATACCACCATCCTTGTAGACTCAGAAAAAGAAGAT
CCAATAAAATACAATGATTACCTAGAAGTGCAAGAAATGACCGACATCACGTGGCTCAAC
TCCCCCAGTCAGGTGGCGGTAGTGCCCTGGGGGTTGCGCAAAGTGCTGAACTGGCTGAAG
TTCAAGTACGGAGACCTCCCCATGTACATAATATCCAATGGAATCGATGACGGGCTGCAT
GCTGAGGACGACCAGCTGAGGGTGTATTATATGCAGAATTACATAAACGAAGCTCTCAAA
GCCCACATACTGGATGGTATCAATCTTTGCGGATACTTTGCTTATTCGTTTAACGACCGC
ACAGCTCCGAGGTTTGGCCTCTATCGTTATGCTGCAGATCAGTTTGAGCCCAAGGCATCC
ATGAAACATTACAGGAAAATTATTGACAGCAATGGTTTCCCGGGCCCAGAAACTCTGGAA
AGATTTTGTCCAGAAGAATTCACCGTGTGTACTGAGTGCAGTTTTTTTCACACCCGAAAG
TCTTTACTGGCTTTCATAGCTTTTCTATTTTTTGCTTCTATTATTTCTCTCTCCCTTATA
TTTTACTACTCGAAGAAAGGCAGAAGAAGTTACAAATAG
GenBank Gene ID
GeneCard IDNone
GenAtlas ID
HGNC IDHGNC:6344
Chromosome Location13
LocusNone
References
  1. 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 Nov 6;390(6655):45-51.[9363890 ]
  2. Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M, Nabeshima Y: Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun. 1998 Jan 26;242(3):626-30.[9464267 ]
  3. Kato Y, Arakawa E, Kinoshita S, Shirai A, Furuya A, Yamano K, Nakamura K, Iida A, Anazawa H, Koh N, Iwano A, Imura A, Fujimori T, Kuro-o M, Hanai N, Takeshige K, Nabeshima Y: Establishment of the anti-Klotho monoclonal antibodies and detection of Klotho protein in kidneys. Biochem Biophys Res Commun. 2000 Jan 19;267(2):597-602.[10631108 ]
  4. Yahata K, Mori K, Arai H, Koide S, Ogawa Y, Mukoyama M, Sugawara A, Ozaki S, Tanaka I, Nabeshima Y, Nakao K: Molecular cloning and expression of a novel klotho-related protein. J Mol Med (Berl). 2000;78(7):389-94.[11043382 ]
  5. Koh N, Fujimori T, Nishiguchi S, Tamori A, Shiomi S, Nakatani T, Sugimura K, Kishimoto T, Kinoshita S, Kuroki T, Nabeshima Y: Severely reduced production of klotho in human chronic renal failure kidney. Biochem Biophys Res Commun. 2001 Feb 2;280(4):1015-20.[11162628 ]
  6. Imura A, Iwano A, Tohyama O, Tsuji Y, Nozaki K, Hashimoto N, Fujimori T, Nabeshima Y: Secreted Klotho protein in sera and CSF: implication for post-translational cleavage in release of Klotho protein from cell membrane. FEBS Lett. 2004 May 7;565(1-3):143-7.[15135068 ]
  7. Arking DE, Krebsova A, Macek M Sr, Macek M Jr, 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 U S A. 2002 Jan 22;99(2):856-61. Epub 2002 Jan 15.[11792841 ]
  8. 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 Mar 4;96(4):412-8. Epub 2005 Jan 27.[15677572 ]
  9. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7.[16959974 ]
  10. Ichikawa S, Imel EA, Kreiter ML, Yu X, Mackenzie DS, Sorenson AH, Goetz R, Mohammadi M, White KE, Econs MJ: A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis. J Clin Invest. 2007 Sep;117(9):2684-91.[17710231 ]
  11. Dunham A, Matthews LH, Burton J, Ashurst JL, Howe KL, Ashcroft KJ, Beare DM, Burford DC, Hunt SE, Griffiths-Jones S, Jones MC, Keenan SJ, Oliver K, Scott CE, Ainscough R, Almeida JP, Ambrose KD, Andrews DT, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Bannerjee R, Barlow KF, Bates K, Beasley H, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burrill W, Carder C, Carter NP, Chapman JC, Clamp ME, Clark SY, Clarke G, Clee CM, Clegg SC, Cobley V, Collins JE, Corby N, Coville GJ, Deloukas P, Dhami P, Dunham I, Dunn M, Earthrowl ME, Ellington AG, Faulkner L, Frankish AG, Frankland J, French L, Garner P, Garnett J, Gilbert JG, Gilson CJ, Ghori J, Grafham DV, Gribble SM, Griffiths C, Hall RE, Hammond S, Harley JL, Hart EA, Heath PD, Howden PJ, Huckle EJ, Hunt PJ, Hunt AR, Johnson C, Johnson D, Kay M, Kimberley AM, King A, Laird GK, Langford CJ, Lawlor S, Leongamornlert DA, Lloyd DM, Lloyd C, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, McLaren SJ, McMurray A, Milne S, Moore MJ, Nickerson T, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter KM, Rice CM, Searle S, Sehra HK, Shownkeen R, Skuce CD, Smith M, Steward CA, Sycamore N, Tester J, Thomas DW, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Wilming L, Wray PW, Wright MW, Young L, Coulson A, Durbin R, Hubbard T, Sulston JE, Beck S, Bentley DR, Rogers J, Ross MT: The DNA sequence and analysis of human chromosome 13. Nature. 2004 Apr 1;428(6982):522-8.[15057823 ]

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