ID KLOT_HUMAN Reviewed; 1012 AA. AC Q9UEF7; Q5VZ95; Q96KV5; Q96KW5; Q9UEI9; Q9Y4F0; DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot. DT 11-OCT-2005, sequence version 2. DT 24-JAN-2024, entry version 182. DE RecName: Full=Klotho; DE EC=3.2.1.31; DE Contains: DE RecName: Full=Klotho peptide; DE Flags: Precursor; GN Name=KL; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT VAL-45. RC TISSUE=Kidney; RX PubMed=9363890; DOI=10.1038/36285; RA Kuro-o M., Matsumura Y., Aizawa H., Kawaguchi H., Suga T., Utsugi T., RA Ohyama Y., Kurabayashi M., Kaname T., Kume E., Iwasaki H., Iida A., RA Shiraki-Iida T., Nishikawa S., Nagai R., Nabeshima Y.; RT "Mutation of the mouse klotho gene leads to a syndrome resembling ageing."; RL Nature 390:45-51(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), VARIANT RP GLN-15, AND TISSUE SPECIFICITY. RC TISSUE=Hippocampus, and Kidney; RX PubMed=9464267; DOI=10.1006/bbrc.1997.8019; RA Matsumura Y., Aizawa H., Shiraki-Iida T., Nagai R., Kuro-o M., RA Nabeshima Y.; RT "Identification of the human klotho gene and its two transcripts encoding RT membrane and secreted klotho protein."; RL Biochem. Biophys. Res. Commun. 242:626-630(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L., RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., RA Frankish A.G., Frankland J., French L., Garner P., Garnett J., RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., RA Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [4] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=10631108; DOI=10.1006/bbrc.1999.2009; RA Kato Y., Arakawa E., Kinoshita S., Shirai A., Furuya A., Yamano K., RA Nakamura K., Iida A., Anazawa H., Koh N., Iwano A., Imura A., Fujimori T., RA Kuro-o M., Hanai N., Takeshige K., Nabeshima Y.; RT "Establishment of the anti-Klotho monoclonal antibodies and detection of RT Klotho protein in kidneys."; RL Biochem. Biophys. Res. Commun. 267:597-602(2000). RN [5] RP TISSUE SPECIFICITY. RX PubMed=11043382; DOI=10.1007/s001090000131; RA Yahata K., Mori K., Arai H., Koide S., Ogawa Y., Mukoyama M., Sugawara A., RA Ozaki S., Tanaka I., Nabeshima Y., Nakao K.; RT "Molecular cloning and expression of a novel klotho-related protein."; RL J. Mol. Med. 78:389-394(2000). RN [6] RP TISSUE SPECIFICITY, AND INVOLVEMENT IN RENAL FAILURE. RX PubMed=11162628; DOI=10.1006/bbrc.2000.4226; RA Koh N., Fujimori T., Nishiguchi S., Tamori A., Shiomi S., Nakatani T., RA Sugimura K., Kishimoto T., Kinoshita S., Kuroki T., Nabeshima Y.; RT "Severely reduced production of klotho in human chronic renal failure RT kidney."; RL Biochem. Biophys. Res. Commun. 280:1015-1020(2001). RN [7] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=15135068; DOI=10.1016/j.febslet.2004.03.090; RA Imura A., Iwano A., Tohyama O., Tsuji Y., Nozaki K., Hashimoto N., RA Fujimori T., Nabeshima Y.; RT "Secreted Klotho protein in sera and CSF: implication for post- RT translational cleavage in release of Klotho protein from cell membrane."; RL FEBS Lett. 565:143-147(2004). RN [8] RP VARIANTS KL-VS VAL-352 AND SER-370. RX PubMed=11792841; DOI=10.1073/pnas.022484299; RA Arking D.E., Krebsova A., Macek M. Sr., Macek M. Jr., Arking A., Mian I.S., RA Fried L., Hamosh A., Dey S., McIntosh I., Dietz H.C.; RT "Association of human aging with a functional variant of klotho."; RL Proc. Natl. Acad. Sci. U.S.A. 99:856-861(2002). RN [9] RP VARIANTS KL-VS VAL-352 AND SER-370. RX PubMed=15677572; DOI=10.1161/01.res.0000157171.04054.30; RA Arking D.E., Atzmon G., Arking A., Barzilai N., Dietz H.C.; RT "Association between a functional variant of the KLOTHO gene and high- RT density lipoprotein cholesterol, blood pressure, stroke, and longevity."; RL Circ. Res. 96:412-418(2005). RN [10] RP VARIANT [LARGE SCALE ANALYSIS] LEU-954. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [11] RP VARIANT HFTC3 ARG-193. RX PubMed=17710231; DOI=10.1172/jci31330; RA Ichikawa S., Imel E.A., Kreiter M.L., Yu X., Mackenzie D.S., Sorenson A.H., RA Goetz R., Mohammadi M., White K.E., Econs M.J.; RT "A homozygous missense mutation in human KLOTHO causes severe tumoral RT calcinosis."; RL J. Clin. Invest. 117:2684-2691(2007). CC -!- FUNCTION: May have weak glycosidase activity towards glucuronylated CC steroids. However, it lacks essential active site Glu residues at CC positions 239 and 872, suggesting it may be inactive as a glycosidase CC in vivo. May be involved in the regulation of calcium and phosphorus CC homeostasis by inhibiting the synthesis of active vitamin D (By CC similarity). Essential factor for the specific interaction between CC FGF23 and FGFR1 (By similarity). {ECO:0000250}. CC -!- FUNCTION: The Klotho peptide generated by cleavage of the membrane- CC bound isoform may be an anti-aging circulating hormone which would CC extend life span by inhibiting insulin/IGF1 signaling. {ECO:0000250}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a beta-D-glucuronoside + H2O = an alcohol + D-glucuronate; CC Xref=Rhea:RHEA:17633, ChEBI:CHEBI:15377, ChEBI:CHEBI:30879, CC ChEBI:CHEBI:58720, ChEBI:CHEBI:83411; EC=3.2.1.31; CC -!- SUBUNIT: Homodimer. Interacts with FGF23 and FGFR1. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane CC {ECO:0000269|PubMed:10631108, ECO:0000269|PubMed:15135068}; Single-pass CC type I membrane protein {ECO:0000305}. Apical cell membrane CC {ECO:0000250|UniProtKB:O35082}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:O35082}. Note=Isoform 1 shedding leads to a CC soluble peptide. {ECO:0000250|UniProtKB:O35082}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted CC {ECO:0000269|PubMed:10631108, ECO:0000269|PubMed:15135068}. CC -!- SUBCELLULAR LOCATION: [Klotho peptide]: Secreted CC {ECO:0000250|UniProtKB:O35082}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=Membrane-bound; CC IsoId=Q9UEF7-1; Sequence=Displayed; CC Name=2; Synonyms=Secreted; CC IsoId=Q9UEF7-2; Sequence=VSP_015824, VSP_015825; CC -!- TISSUE SPECIFICITY: Present in cortical renal tubules (at protein CC level). Soluble peptide is present in serum and cerebrospinal fluid. CC Expressed in kidney, placenta, small intestine and prostate. Down- CC regulated in renal cell carcinomas, hepatocellular carcinomas, and in CC chronic renal failure kidney. {ECO:0000269|PubMed:10631108, CC ECO:0000269|PubMed:11043382, ECO:0000269|PubMed:11162628, CC ECO:0000269|PubMed:15135068, ECO:0000269|PubMed:9464267}. CC -!- DOMAIN: Contains 2 glycosyl hydrolase 1 regions. However, the first CC region lacks the essential Glu active site residue at position 239, and CC the second one lacks the essential Glu active site residue at position CC 872. CC -!- PTM: N-glycosylated. {ECO:0000250}. CC -!- POLYMORPHISM: Homozygosity for KL-VS allele is associated with CC decreased longevity and increased cardiovascular disease risk. CC {ECO:0000269|PubMed:11792841, ECO:0000269|PubMed:15677572}. CC -!- DISEASE: Tumoral calcinosis, hyperphosphatemic, familial, 3 (HFTC3) CC [MIM:617994]: A form of hyperphosphatemic tumoral calcinosis, a rare CC autosomal recessive metabolic disorder that manifests with CC hyperphosphatemia and massive calcium deposits in the skin and CC subcutaneous tissues. Some patients have recurrent, transient, painful CC swellings of the long bones associated with the radiographic findings CC of periosteal reaction and cortical hyperostosis and absence of skin CC involvement. {ECO:0000269|PubMed:17710231}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Defects in KL may be a cause of chronic renal failure CC complications. CC -!- MISCELLANEOUS: [Isoform 2]: Predominates over the membrane form in all CC tissues examined. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 1 family. Klotho CC subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The thread of life - Issue CC 65 of December 2005; CC URL="https://web.expasy.org/spotlight/back_issues/065"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB005142; BAA23382.1; -; mRNA. DR EMBL; AB009667; BAA24940.1; -; Genomic_DNA. DR EMBL; AB009667; BAA24941.1; -; Genomic_DNA. DR EMBL; AL161898; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; Z92540; CAC94767.1; -; Genomic_DNA. DR EMBL; Z84483; CAC94773.1; -; Genomic_DNA. DR CCDS; CCDS9347.1; -. [Q9UEF7-1] DR PIR; JC5925; JC5925. DR PIR; JC5926; JC5926. DR RefSeq; NP_004786.2; NM_004795.3. [Q9UEF7-1] DR PDB; 5W21; X-ray; 3.00 A; A=1-981. DR PDB; 7YSH; EM; 2.74 A; A=34-981. DR PDB; 7YSU; EM; 3.20 A; A=34-975. DR PDB; 7YSW; EM; 3.03 A; A=34-975. DR PDBsum; 5W21; -. DR PDBsum; 7YSH; -. DR PDBsum; 7YSU; -. DR PDBsum; 7YSW; -. DR AlphaFoldDB; Q9UEF7; -. DR EMDB; EMD-34075; -. DR EMDB; EMD-34082; -. DR EMDB; EMD-34084; -. DR SMR; Q9UEF7; -. DR BioGRID; 114766; 4. DR IntAct; Q9UEF7; 2. DR STRING; 9606.ENSP00000369442; -. DR ChEMBL; CHEMBL4523485; -. DR CAZy; GH1; Glycoside Hydrolase Family 1. DR TCDB; 8.A.49.1.1; the klotho auxiliary protein (klotho) family. DR GlyConnect; 1435; 1 N-Linked glycan (1 site). DR GlyCosmos; Q9UEF7; 8 sites, 2 glycans. DR GlyGen; Q9UEF7; 9 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site). DR iPTMnet; Q9UEF7; -. DR PhosphoSitePlus; Q9UEF7; -. DR BioMuta; KL; -. DR DMDM; 77416517; -. DR jPOST; Q9UEF7; -. DR MassIVE; Q9UEF7; -. DR PaxDb; 9606-ENSP00000369442; -. DR PeptideAtlas; Q9UEF7; -. DR ProteomicsDB; 84144; -. [Q9UEF7-1] DR ProteomicsDB; 84145; -. [Q9UEF7-2] DR ABCD; Q9UEF7; 1 sequenced antibody. DR Antibodypedia; 7860; 447 antibodies from 40 providers. DR DNASU; 9365; -. DR Ensembl; ENST00000380099.4; ENSP00000369442.3; ENSG00000133116.8. [Q9UEF7-1] DR GeneID; 9365; -. DR KEGG; hsa:9365; -. DR MANE-Select; ENST00000380099.4; ENSP00000369442.3; NM_004795.4; NP_004786.2. DR UCSC; uc001uus.3; human. [Q9UEF7-1] DR AGR; HGNC:6344; -. DR CTD; 9365; -. DR DisGeNET; 9365; -. DR GeneCards; KL; -. DR GeneReviews; KL; -. DR HGNC; HGNC:6344; KL. DR HPA; ENSG00000133116; Group enriched (kidney, parathyroid gland). DR MalaCards; KL; -. DR MIM; 604824; gene. DR MIM; 617994; phenotype. DR neXtProt; NX_Q9UEF7; -. DR OpenTargets; ENSG00000133116; -. DR Orphanet; 306661; Familial hyperphosphatemic tumoral calcinosis/Hyperphosphatemic hyperostosis syndrome. DR PharmGKB; PA30130; -. DR VEuPathDB; HostDB:ENSG00000133116; -. DR eggNOG; KOG0626; Eukaryota. DR GeneTree; ENSGT00940000157614; -. DR HOGENOM; CLU_001859_5_2_1; -. DR InParanoid; Q9UEF7; -. DR OMA; HVSHFHF; -. DR OrthoDB; 3373839at2759; -. DR PhylomeDB; Q9UEF7; -. DR TreeFam; TF314803; -. DR PathwayCommons; Q9UEF7; -. DR Reactome; R-HSA-109704; PI3K Cascade. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-190374; FGFR1c and Klotho ligand binding and activation. DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. DR Reactome; R-HSA-5654219; Phospholipase C-mediated cascade: FGFR1. DR Reactome; R-HSA-5654687; Downstream signaling of activated FGFR1. DR Reactome; R-HSA-5654688; SHC-mediated cascade:FGFR1. DR Reactome; R-HSA-5654689; PI-3K cascade:FGFR1. DR Reactome; R-HSA-5654693; FRS-mediated FGFR1 signaling. DR Reactome; R-HSA-5654726; Negative regulation of FGFR1 signaling. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR SignaLink; Q9UEF7; -. DR BioGRID-ORCS; 9365; 12 hits in 1150 CRISPR screens. DR ChiTaRS; KL; human. DR GeneWiki; Klotho_(biology); -. DR GenomeRNAi; 9365; -. DR Pharos; Q9UEF7; Tbio. DR PRO; PR:Q9UEF7; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; Q9UEF7; Protein. DR Bgee; ENSG00000133116; Expressed in choroid plexus epithelium and 123 other cell types or tissues. DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; TAS:UniProtKB. DR GO; GO:0016020; C:membrane; TAS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0008422; F:beta-glucosidase activity; TAS:ProtInc. DR GO; GO:0004566; F:beta-glucuronidase activity; IEA:UniProtKB-EC. DR GO; GO:0017134; F:fibroblast growth factor binding; IPI:UniProtKB. DR GO; GO:0005104; F:fibroblast growth factor receptor binding; IBA:GO_Central. DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW. DR GO; GO:0005499; F:vitamin D binding; IEA:UniProtKB-KW. DR GO; GO:0055074; P:calcium ion homeostasis; IEA:Ensembl. DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro. DR GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl. DR GO; GO:0006112; P:energy reserve metabolic process; IEA:Ensembl. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IBA:GO_Central. DR GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; IEA:Ensembl. DR GO; GO:0042421; P:norepinephrine biosynthetic process; IEA:Ensembl. DR GO; GO:0030501; P:positive regulation of bone mineralization; IMP:UniProtKB. DR GO; GO:0090080; P:positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway; IEA:Ensembl. DR GO; GO:0014823; P:response to activity; IEA:Ensembl. DR GO; GO:1990776; P:response to angiotensin; IEA:Ensembl. DR GO; GO:0033280; P:response to vitamin D; IEA:Ensembl. DR Gene3D; 3.20.20.80; Glycosidases; 2. DR InterPro; IPR001360; Glyco_hydro_1. DR InterPro; IPR033132; Glyco_hydro_1_N_CS. DR InterPro; IPR017853; Glycoside_hydrolase_SF. DR PANTHER; PTHR10353; GLYCOSYL HYDROLASE; 1. DR PANTHER; PTHR10353:SF10; KLOTHO; 1. DR Pfam; PF00232; Glyco_hydro_1; 4. DR PRINTS; PR00131; GLHYDRLASE1. DR SUPFAM; SSF51445; (Trans)glycosidases; 2. DR PROSITE; PS00653; GLYCOSYL_HYDROL_F1_2; 1. DR Genevisible; Q9UEF7; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disease variant; KW Glycoprotein; Glycosidase; Hormone; Hydrolase; Membrane; KW Reference proteome; Repeat; Secreted; Signal; Transmembrane; KW Transmembrane helix; Vitamin D. FT SIGNAL 1..33 FT /evidence="ECO:0000255" FT CHAIN 34..1012 FT /note="Klotho" FT /id="PRO_0000042243" FT CHAIN 34..? FT /note="Klotho peptide" FT /evidence="ECO:0000250" FT /id="PRO_0000042244" FT TOPO_DOM 34..981 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 982..1002 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1003..1012 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 57..506 FT /note="Glycosyl hydrolase-1 1" FT REGION 515..953 FT /note="Glycosyl hydrolase-1 2" FT CARBOHYD 106 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 159 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 283 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 344 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 607 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 612 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 694 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 535..549 FT /note="DTTLSQFTDLNVYLW -> SQLTKPISSLTKPYH (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9464267" FT /id="VSP_015824" FT VAR_SEQ 550..1012 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9464267" FT /id="VSP_015825" FT VARIANT 15 FT /note="P -> Q (in dbSNP:rs1052018)" FT /evidence="ECO:0000269|PubMed:9464267" FT /id="VAR_023582" FT VARIANT 45 FT /note="F -> V (in dbSNP:rs1052019)" FT /evidence="ECO:0000269|PubMed:9363890" FT /id="VAR_023583" FT VARIANT 193 FT /note="H -> R (in HFTC3; impairs the ability to form a FT ternary complex with FGF23 and FGFR1c; impairs KL-dependent FT FGF23 signaling; dbSNP:rs121908423)" FT /evidence="ECO:0000269|PubMed:17710231" FT /id="VAR_064554" FT VARIANT 352 FT /note="F -> V (in allele KL-VS; dbSNP:rs9536314)" FT /evidence="ECO:0000269|PubMed:11792841, FT ECO:0000269|PubMed:15677572" FT /id="VAR_023584" FT VARIANT 370 FT /note="C -> S (in allele KL-VS; dbSNP:rs9527025)" FT /evidence="ECO:0000269|PubMed:11792841, FT ECO:0000269|PubMed:15677572" FT /id="VAR_023585" FT VARIANT 514 FT /note="P -> S (in dbSNP:rs3752472)" FT /id="VAR_049295" FT VARIANT 954 FT /note="P -> L (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs139939367)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036449" FT HELIX 37..40 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 41..44 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 45..47 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 51..54 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 66..70 FT /evidence="ECO:0007829|PDB:7YSH" FT TURN 74..77 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 82..84 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 90..93 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 122..126 FT /evidence="ECO:0007829|PDB:7YSH" FT TURN 128..130 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 132..142 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 145..150 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 153..156 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 157..159 FT /evidence="ECO:0007829|PDB:7YSW" FT STRAND 161..163 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 167..183 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 186..194 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 198..204 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 206..208 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 209..211 FT /evidence="ECO:0007829|PDB:7YSU" FT HELIX 212..227 FT /evidence="ECO:0007829|PDB:7YSH" FT TURN 228..230 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 233..238 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 240..247 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 248..253 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 261..285 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 287..290 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 293..299 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 302..304 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 306..308 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 310..323 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 325..332 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 333..336 FT /evidence="ECO:0007829|PDB:5W21" FT HELIX 339..342 FT /evidence="ECO:0007829|PDB:7YSH" FT TURN 346..348 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 355..359 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 360..362 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 365..372 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 375..379 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 382..385 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 389..391 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 394..404 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 409..415 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 419..422 FT /evidence="ECO:0007829|PDB:7YSW" FT HELIX 428..446 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 451..458 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 466..468 FT /evidence="ECO:0007829|PDB:5W21" FT STRAND 471..473 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 476..478 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 483..485 FT /evidence="ECO:0007829|PDB:5W21" FT HELIX 492..503 FT /evidence="ECO:0007829|PDB:7YSH" FT TURN 510..512 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 524..531 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 539..541 FT /evidence="ECO:0007829|PDB:5W21" FT STRAND 545..549 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 552..554 FT /evidence="ECO:0007829|PDB:5W21" FT STRAND 557..564 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 572..575 FT /evidence="ECO:0007829|PDB:7YSH" FT TURN 576..578 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 579..587 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 591..596 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 599..602 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 603..607 FT /evidence="ECO:0007829|PDB:7YSU" FT HELIX 608..610 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 613..628 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 632..638 FT /evidence="ECO:0007829|PDB:7YSH" FT TURN 643..646 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 649..652 FT /evidence="ECO:0007829|PDB:7YSH" FT TURN 653..657 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 660..676 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 677..679 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 683..688 FT /evidence="ECO:0007829|PDB:7YSH" FT TURN 692..694 FT /evidence="ECO:0007829|PDB:5W21" FT HELIX 697..717 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 719..722 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 725..731 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 734..739 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 743..756 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 758..765 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 766..769 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 772..779 FT /evidence="ECO:0007829|PDB:7YSH" FT TURN 780..782 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 791..797 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 802..807 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 811..817 FT /evidence="ECO:0007829|PDB:7YSH" FT TURN 821..823 FT /evidence="ECO:0007829|PDB:7YSH" FT TURN 826..829 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 830..833 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 838..840 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 850..863 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 867..873 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 879..881 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 882..903 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 908..915 FT /evidence="ECO:0007829|PDB:7YSH" FT TURN 919..921 FT /evidence="ECO:0007829|PDB:7YSH" FT TURN 923..925 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 927..931 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 934..937 FT /evidence="ECO:0007829|PDB:7YSH" FT HELIX 939..950 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 971..973 FT /evidence="ECO:0007829|PDB:7YSU" SQ SEQUENCE 1012 AA; 116181 MW; 62031BD73E322E63 CRC64; MPASAPPRRP RPPPPSLSLL LVLLGLGGRR LRAEPGDGAQ TWARFSRPPA PEAAGLFQGT FPDGFLWAVG SAAYQTEGGW QQHGKGASIW DTFTHHPLAP PGDSRNASLP LGAPSPLQPA TGDVASDSYN NVFRDTEALR ELGVTHYRFS ISWARVLPNG SAGVPNREGL RYYRRLLERL RELGVQPVVT LYHWDLPQRL QDAYGGWANR ALADHFRDYA ELCFRHFGGQ VKYWITIDNP YVVAWHGYAT GRLAPGIRGS PRLGYLVAHN LLLAHAKVWH LYNTSFRPTQ GGQVSIALSS HWINPRRMTD HSIKECQKSL DFVLGWFAKP VFIDGDYPES MKNNLSSILP DFTESEKKFI KGTADFFALC FGPTLSFQLL DPHMKFRQLE SPNLRQLLSW IDLEFNHPQI FIVENGWFVS GTTKRDDAKY MYYLKKFIME TLKAIKLDGV DVIGYTAWSL MDGFEWHRGY SIRRGLFYVD FLSQDKMLLP KSSALFYQKL IEKNGFPPLP ENQPLEGTFP CDFAWGVVDN YIQVDTTLSQ FTDLNVYLWD VHHSKRLIKV DGVVTKKRKS YCVDFAAIQP QIALLQEMHV THFRFSLDWA LILPLGNQSQ VNHTILQYYR CMASELVRVN ITPVVALWQP MAPNQGLPRL LARQGAWENP YTALAFAEYA RLCFQELGHH VKLWITMNEP YTRNMTYSAG HNLLKAHALA WHVYNEKFRH AQNGKISIAL QADWIEPACP FSQKDKEVAE RVLEFDIGWL AEPIFGSGDY PWVMRDWLNQ RNNFLLPYFT EDEKKLIQGT FDFLALSHYT TILVDSEKED PIKYNDYLEV QEMTDITWLN SPSQVAVVPW GLRKVLNWLK FKYGDLPMYI ISNGIDDGLH AEDDQLRVYY MQNYINEALK AHILDGINLC GYFAYSFNDR TAPRFGLYRY AADQFEPKAS MKHYRKIIDS NGFPGPETLE RFCPEEFTVC TECSFFHTRK SLLAFIAFLF FASIISLSLI FYYSKKGRRS YK //