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Identification
HMDB Protein ID HMDBP07765
Secondary Accession Numbers
  • 13474
Name Klotho
Synonyms
  1. Klotho peptide
Gene Name KL
Protein Type Unknown
Biological Properties
General Function Involved in hydrolase activity, hydrolyzing O-glycosyl compounds
Specific Function May 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 (By similarity).
Pathways
  • Endocrine and other factor-regulated calcium reabsorption
  • Pentose and glucuronate interconversions
  • Starch and sucrose metabolism
Reactions
A beta-D-glucuronoside + Water → D-Glucuronic acid + an alcohol details
Water + beta-D-Glucuronoside → D-Glucuronic acid + Alcohol details
GO Classification
Biological Process
positive regulation of bone mineralization
positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway
acute inflammatory response
insulin receptor signaling pathway
energy reserve metabolic process
aging
carbohydrate metabolic process
fibroblast growth factor receptor signaling pathway
Cellular Component
extracellular region
extracellular space
integral to membrane
integral to plasma membrane
Function
ion binding
cation binding
binding
catalytic activity
hydrolase activity
hydrolase activity, acting on glycosyl bonds
hydrolase activity, hydrolyzing o-glycosyl compounds
Molecular Function
vitamin D binding
beta-glucuronidase activity
cation binding
beta-glucosidase activity
signal transducer activity
Process
metabolic process
primary metabolic process
carbohydrate metabolic process
Cellular Location
  1. Klotho peptide:Secreted
Gene Properties
Chromosome Location 13
Locus 13q12
SNPs KL
Gene Sequence
>3039 bp
ATGCCCGCCAGCGCCCCGCCGCGCCGCCCGCGGCCGCCGCCGCCGTCGCTGTCGCTGCTG
CTGGTGCTGCTGGGCCTGGGCGGCCGCCGCCTGCGTGCGGAGCCGGGCGACGGCGCGCAG
ACCTGGGCCCGTGTCTCGCGGCCTCCTGCCCCCGAGGCCGCGGGCCTCTTCCAGGGCACC
TTCCCCGACGGCTTCCTCTGGGCCGTGGGCAGCGCCGCCTACCAGACCGAGGGCGGCTGG
CAGCAGCACGGCAAGGGTGCGTCCATCTGGGACACGTTCACCCACCACCCCCTGGCACCC
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
TTCTCCCAAAAGGACAAAGAGGTGGCCGAGAGAGTTTTGGAATTTGACATTGGCTGGCTG
GCTGAGCCCATTTTCGGCTCTGGAGATTATCCATGGGTGATGAGGGACTGGCTGAACCAA
AGAAACAATTTTCTTCTTCCTTATTTCACTGAAGATGAAAAAAAGCTAATCCAGGGTACC
TTTGACTTTTTGGCTTTAAGCCATTATACCACCATCCTTGTAGACTCAGAAAAAGAAGAT
CCAATAAAATACAATGATTACCTAGAAGTGCAAGAAATGACCGACATCACGTGGCTCAAC
TCCCCCAGTCAGGTGGCGGTAGTGCCCTGGGGGTTGCGCAAAGTGCTGAACTGGCTGAAG
TTCAAGTACGGAGACCTCCCCATGTACATAATATCCAACGGAATCGATGACGGGCTGCAT
GCTGAGGACGACCAGCTGAGGGTGTATTATATGCAGAATTACATAAACGAAGCTCTCAAA
GCCCACATACTGGATGGTATCAATCTTTGCGGATACTTTGCTTATTCGTTTAACGACCGC
ACAGCTCCGAGGTTTGGCCTCTATCGTTATGCTGCAGATCAGTTTGAGCCCAAGGCATCC
ATGAAACATTACAGGAAAATTATTGACAGCAATGGTTTCCCGGGCCCAGAAACTCTGGAA
AGATTTTGTCCAGAAGAATTCACCGTGTGTACTGAGTGCAGTTTTTTTCACACCCGAAAG
TCTTTACTGGCTTTCATAGCTTTTCTATTTTTTGCTTCTATTATTTCTCTCTCCCTTATA
TTTTACTACTCGAAGAAAGGCAGAAGAAGTTACAAATAG
Protein Properties
Number of Residues 1012
Molecular Weight 116179.815
Theoretical pI 7.967
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Klotho
MPASAPPRRPRPPPPSLSLLLVLLGLGGRRLRAEPGDGAQTWARFSRPPAPEAAGLFQGT
FPDGFLWAVGSAAYQTEGGWQQHGKGASIWDTFTHHPLAPPGDSRNASLPLGAPSPLQPA
TGDVASDSYNNVFRDTEALRELGVTHYRFSISWARVLPNGSAGVPNREGLRYYRRLLERL
RELGVQPVVTLYHWDLPQRLQDAYGGWANRALADHFRDYAELCFRHFGGQVKYWITIDNP
YVVAWHGYATGRLAPGIRGSPRLGYLVAHNLLLAHAKVWHLYNTSFRPTQGGQVSIALSS
HWINPRRMTDHSIKECQKSLDFVLGWFAKPVFIDGDYPESMKNNLSSILPDFTESEKKFI
KGTADFFALCFGPTLSFQLLDPHMKFRQLESPNLRQLLSWIDLEFNHPQIFIVENGWFVS
GTTKRDDAKYMYYLKKFIMETLKAIKLDGVDVIGYTAWSLMDGFEWHRGYSIRRGLFYVD
FLSQDKMLLPKSSALFYQKLIEKNGFPPLPENQPLEGTFPCDFAWGVVDNYIQVDTTLSQ
FTDLNVYLWDVHHSKRLIKVDGVVTKKRKSYCVDFAAIQPQIALLQEMHVTHFRFSLDWA
LILPLGNQSQVNHTILQYYRCMASELVRVNITPVVALWQPMAPNQGLPRLLARQGAWENP
YTALAFAEYARLCFQELGHHVKLWITMNEPYTRNMTYSAGHNLLKAHALAWHVYNEKFRH
AQNGKISIALQADWIEPACPFSQKDKEVAERVLEFDIGWLAEPIFGSGDYPWVMRDWLNQ
RNNFLLPYFTEDEKKLIQGTFDFLALSHYTTILVDSEKEDPIKYNDYLEVQEMTDITWLN
SPSQVAVVPWGLRKVLNWLKFKYGDLPMYIISNGIDDGLHAEDDQLRVYYMQNYINEALK
AHILDGINLCGYFAYSFNDRTAPRFGLYRYAADQFEPKASMKHYRKIIDSNGFPGPETLE
RFCPEEFTVCTECSFFHTRKSLLAFIAFLFFASIISLSLIFYYSKKGRRSYK
GenBank ID Protein 2618596
UniProtKB/Swiss-Prot ID Q9UEF7
UniProtKB/Swiss-Prot Entry Name KLOT_HUMAN
PDB IDs Not Available
GenBank Gene ID AB005142
GeneCard ID KL
GenAtlas ID KL
HGNC ID HGNC:6344
References
General References
  1. 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. [PubMed:16959974 ]
  2. 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. [PubMed:15057823 ]
  3. 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. [PubMed:11043382 ]
  4. 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. [PubMed:9363890 ]
  5. 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. [PubMed:9464267 ]
  6. 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. [PubMed:10631108 ]
  7. 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. [PubMed:11162628 ]
  8. 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. [PubMed:15135068 ]
  9. 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. [PubMed:11792841 ]
  10. 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. [PubMed:15677572 ]