KLOT_HUMAN
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 03-AUG-2022, entry version 174.
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";
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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 PDBsum; 5W21; -.
DR AlphaFoldDB; Q9UEF7; -.
DR SMR; Q9UEF7; -.
DR BioGRID; 114766; 1.
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 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; Q9UEF7; -.
DR PeptideAtlas; Q9UEF7; -.
DR PRIDE; Q9UEF7; -.
DR ProteomicsDB; 84144; -. [Q9UEF7-1]
DR ProteomicsDB; 84145; -. [Q9UEF7-2]
DR ABCD; Q9UEF7; 1 sequenced antibody.
DR Antibodypedia; 7860; 392 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 CTD; 9365; -.
DR DisGeNET; 9365; -.
DR GeneCards; KL; -.
DR GeneReviews; KL; -.
DR HGNC; HGNC:6344; KL.
DR HPA; ENSG00000133116; Tissue enhanced (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; LHYYRCV; -.
DR OrthoDB; 408001at2759; -.
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; 10 hits in 1072 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 122 other tissues.
DR Genevisible; Q9UEF7; HS.
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:0016021; C:integral component of membrane; TAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
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:0002526; P:acute inflammatory response; IEA:Ensembl.
DR GO; GO:0007568; P:aging; IMP:UniProtKB.
DR GO; GO:0055074; P:calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
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:0008286; P:insulin receptor signaling pathway; IEA:InterPro.
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 InterPro; IPR001360; Glyco_hydro_1.
DR InterPro; IPR033132; Glyco_hydro_1_N_CS.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR InterPro; IPR028546; Klotho.
DR PANTHER; PTHR10353; PTHR10353; 5.
DR PANTHER; PTHR10353:SF10; PTHR10353:SF10; 5.
DR Pfam; PF00232; Glyco_hydro_1; 3.
DR PRINTS; PR00131; GLHYDRLASE1.
DR SUPFAM; SSF51445; SSF51445; 2.
DR PROSITE; PS00653; GLYCOSYL_HYDROL_F1_2; 1.
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; associated with S-370;
FT 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; associated with V-352;
FT 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 TURN 35..40
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 41..44
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 51..55
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 66..70
FT /evidence="ECO:0007829|PDB:5W21"
FT TURN 74..77
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 89..95
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 133..142
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 145..150
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 153..156
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 167..183
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 186..194
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 199..202
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 206..208
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 212..226
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 227..229
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 233..238
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 240..248
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 261..283
FT /evidence="ECO:0007829|PDB:5W21"
FT TURN 284..286
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 287..290
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 293..299
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 310..323
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 325..332
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 333..336
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 339..344
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 346..349
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 354..360
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 365..370
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 375..379
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 383..385
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 389..391
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 395..404
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 410..414
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 428..446
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 452..458
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 466..468
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 471..473
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 476..478
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 483..485
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 492..503
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 510..512
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 524..529
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 539..541
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 546..549
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 552..554
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 557..559
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 578..587
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 591..596
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 599..602
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 606..610
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 613..628
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 632..638
FT /evidence="ECO:0007829|PDB:5W21"
FT TURN 642..646
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 649..653
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 656..658
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 661..676
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 677..679
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 683..689
FT /evidence="ECO:0007829|PDB:5W21"
FT TURN 692..694
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 697..717
FT /evidence="ECO:0007829|PDB:5W21"
FT TURN 718..721
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 725..731
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 734..739
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 743..756
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 758..765
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 766..769
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 772..780
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 791..797
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 802..807
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 811..817
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 821..823
FT /evidence="ECO:0007829|PDB:5W21"
FT TURN 826..829
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 830..833
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 849..863
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 868..873
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 884..903
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 909..915
FT /evidence="ECO:0007829|PDB:5W21"
FT TURN 919..921
FT /evidence="ECO:0007829|PDB:5W21"
FT TURN 923..925
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 927..933
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 935..937
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 939..950
FT /evidence="ECO:0007829|PDB:5W21"
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
