FGF23_HUMAN
ID FGF23_HUMAN Reviewed; 251 AA.
AC Q9GZV9; Q4V758;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Fibroblast growth factor 23;
DE Short=FGF-23;
DE AltName: Full=Phosphatonin;
DE AltName: Full=Tumor-derived hypophosphatemia-inducing factor;
DE Contains:
DE RecName: Full=Fibroblast growth factor 23 N-terminal peptide;
DE Contains:
DE RecName: Full=Fibroblast growth factor 23 C-terminal peptide;
DE Flags: Precursor;
GN Name=FGF23; Synonyms=HYPF; ORFNames=UNQ3027/PRO9828;
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].
RX PubMed=11032749; DOI=10.1006/bbrc.2000.3696;
RA Yamashita T., Yoshioka M., Itoh N.;
RT "Identification of a novel fibroblast growth factor, FGF-23, preferentially
RT expressed in the ventrolateral thalamic nucleus of the brain.";
RL Biochem. Biophys. Res. Commun. 277:494-498(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, VARIANTS ADHR GLN-176; GLN-179 AND
RP TRP-179, AND VARIANT MET-239.
RX PubMed=11062477; DOI=10.1038/81664;
RA White K.E., Evans W.E., O'Riordan J.L.H., Speer M.C., Econs M.J.,
RA Lorenz-Depiereux B., Grabowski M., Meitinger T., Strom T.M.;
RT "Autosomal dominant hypophosphataemic rickets is associated with mutations
RT in FGF23.";
RL Nat. Genet. 26:345-348(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11344269; DOI=10.1073/pnas.101545198;
RA Shimada T., Mizutani S., Muto T., Yoneya T., Hino R., Takeda S.,
RA Takeuchi Y., Fujita T., Fukumoto S., Yamashita T.;
RT "Cloning and characterization of FGF23 as a causative factor of tumor-
RT induced osteomalacia.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:6500-6505(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-195 AND MET-239.
RG NIEHS SNPs program;
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 25-39.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [8]
RP FUNCTION, AND CHARACTERIZATION OF VARIANT ADHR GLN-179.
RX PubMed=11409890; DOI=10.1006/bbrc.2001.5084;
RA Bowe A.E., Finnegan R., Jan de Beur S.M., Cho J., Levine M.A., Kumar R.,
RA Schiavi S.C.;
RT "FGF-23 inhibits renal tubular phosphate transport and is a PHEX
RT substrate.";
RL Biochem. Biophys. Res. Commun. 284:977-981(2001).
RN [9]
RP PROTEOLYTIC PROCESSING.
RX PubMed=11157998; DOI=10.1210/jcem.86.2.7408;
RA White K.E., Jonsson K.B., Carn G., Hampson G., Spector T.D., Mannstadt M.,
RA Lorenz-Depiereux B., Miyauchi A., Yang I.M., Ljunggren O., Meitinger T.,
RA Strom T.M., Jueppner H., Econs M.J.;
RT "The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted
RT polypeptide overexpressed by tumors that cause phosphate wasting.";
RL J. Clin. Endocrinol. Metab. 86:497-500(2001).
RN [10]
RP PROTEOLYTIC PROCESSING.
RX PubMed=12130585; DOI=10.1210/endo.143.8.8795;
RA Shimada T., Muto T., Urakawa I., Yoneya T., Yamazaki Y., Okawa K.,
RA Takeuchi Y., Fujita T., Fukumoto S., Yamashita T.;
RT "Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets
RT is resistant to proteolytic cleavage and causes hypophosphatemia in vivo.";
RL Endocrinology 143:3179-3182(2002).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=12952917; DOI=10.1172/jci200318399;
RA Riminucci M., Collins M.T., Fedarko N.S., Cherman N., Corsi A., White K.E.,
RA Waguespack S., Gupta A., Hannon T., Econs M.J., Bianco P., Gehron Robey P.;
RT "FGF-23 in fibrous dysplasia of bone and its relationship to renal
RT phosphate wasting.";
RL J. Clin. Invest. 112:683-692(2003).
RN [12]
RP PROTEOLYTIC PROCESSING BY PROPROTEIN CONVERTASES.
RX PubMed=15268897; DOI=10.1016/j.bone.2004.04.002;
RA Benet-Pages A., Lorenz-Depiereux B., Zischka H., White K.E., Econs M.J.,
RA Strom T.M.;
RT "FGF23 is processed by proprotein convertases but not by PHEX.";
RL Bone 35:455-462(2004).
RN [13]
RP FUNCTION.
RX PubMed=15040831; DOI=10.1359/jbmr.0301264;
RA Shimada T., Hasegawa H., Yamazaki Y., Muto T., Hino R., Takeuchi Y.,
RA Fujita T., Nakahara K., Fukumoto S., Yamashita T.;
RT "FGF-23 is a potent regulator of vitamin D metabolism and phosphate
RT homeostasis.";
RL J. Bone Miner. Res. 19:429-435(2004).
RN [14]
RP INTERACTION WITH FGFR1; FGFR2; FGFR3 AND FGFR4, AND FUNCTION IN STIMULATION
RP OF CELL PROLIFERATION.
RX PubMed=16597617; DOI=10.1074/jbc.m601252200;
RA Zhang X., Ibrahimi O.A., Olsen S.K., Umemori H., Mohammadi M., Ornitz D.M.;
RT "Receptor specificity of the fibroblast growth factor family. The complete
RT mammalian FGF family.";
RL J. Biol. Chem. 281:15694-15700(2006).
RN [15]
RP SUBCELLULAR LOCATION, GLYCOSYLATION AT THR-178, CHARACTERIZATION OF
RP VARIANTS ADHR GLN-176 AND GLN-179, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16638743; DOI=10.1074/jbc.m602469200;
RA Kato K., Jeanneau C., Tarp M.A., Benet-Pages A., Lorenz-Depiereux B.,
RA Bennett E.P., Mandel U., Strom T.M., Clausen H.;
RT "Polypeptide GalNAc-transferase T3 and familial tumoral calcinosis.
RT Secretion of fibroblast growth factor 23 requires O-glycosylation.";
RL J. Biol. Chem. 281:18370-18377(2006).
RN [16]
RP FUNCTION.
RX PubMed=18282132; DOI=10.1359/jbmr.080220;
RA Wang H., Yoshiko Y., Yamamoto R., Minamizaki T., Kozai K., Tanne K.,
RA Aubin J.E., Maeda N.;
RT "Overexpression of fibroblast growth factor 23 suppresses osteoblast
RT differentiation and matrix mineralization in vitro.";
RL J. Bone Miner. Res. 23:939-948(2008).
RN [17]
RP REVIEW.
RX PubMed=20094046; DOI=10.1038/nrc2780;
RA Turner N., Grose R.;
RT "Fibroblast growth factor signalling: from development to cancer.";
RL Nat. Rev. Cancer 10:116-129(2010).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 25-179.
RX PubMed=17339340; DOI=10.1128/mcb.02249-06;
RA Goetz R., Beenken A., Ibrahimi O.A., Kalinina J., Olsen S.K.,
RA Eliseenkova A.V., Xu C., Neubert T.A., Zhang F., Linhardt R.J., Yu X.,
RA White K.E., Inagaki T., Kliewer S.A., Yamamoto M., Kurosu H., Ogawa Y.,
RA Kuro-o M., Lanske B., Razzaque M.S., Mohammadi M.;
RT "Molecular insights into the klotho-dependent, endocrine mode of action of
RT fibroblast growth factor 19 subfamily members.";
RL Mol. Cell. Biol. 27:3417-3428(2007).
RN [19]
RP VARIANT HFTC2 THR-96.
RX PubMed=16151858; DOI=10.1007/s00439-005-0026-8;
RA Chefetz I., Heller R., Galli-Tsinopoulou A., Richard G., Wollnik B.,
RA Indelman M., Koerber F., Topaz O., Bergman R., Sprecher E., Schoenau E.;
RT "A novel homozygous missense mutation in FGF23 causes Familial Tumoral
RT Calcinosis associated with disseminated visceral calcification.";
RL Hum. Genet. 118:261-266(2005).
RN [20]
RP VARIANT HFTC2 GLY-71.
RX PubMed=15590700; DOI=10.1093/hmg/ddi034;
RA Benet-Pages A., Orlik P., Strom T.M., Lorenz-Depiereux B.;
RT "An FGF23 missense mutation causes familial tumoral calcinosis with
RT hyperphosphatemia.";
RL Hum. Mol. Genet. 14:385-390(2005).
RN [21]
RP VARIANT HFTC2 PHE-129, AND CHARACTERIZATION OF VARIANT HFTC2 PHE-129.
RX PubMed=16030159; DOI=10.1210/jc.2005-0301;
RA Araya K., Fukumoto S., Backenroth R., Takeuchi Y., Nakayama K., Ito N.,
RA Yoshii N., Yamazaki Y., Yamashita T., Silver J., Igarashi T., Fujita T.;
RT "A novel mutation in fibroblast growth factor 23 gene as a cause of tumoral
RT calcinosis.";
RL J. Clin. Endocrinol. Metab. 90:5523-5527(2005).
RN [22]
RP VARIANT HFTC2 LEU-157.
RX PubMed=24680727; DOI=10.1016/j.gene.2014.03.052;
RA Abbasi F., Ghafouri-Fard S., Javaheri M., Dideban A., Ebrahimi A.,
RA Ebrahim-Habibi A.;
RT "A new missense mutation in FGF23 gene in a male with hyperostosis-
RT hyperphosphatemia syndrome (HHS).";
RL Gene 542:269-271(2014).
CC -!- FUNCTION: Regulator of phosphate homeostasis. Inhibits renal tubular
CC phosphate transport by reducing SLC34A1 levels. Up-regulates EGR1
CC expression in the presence of KL (By similarity). Acts directly on the
CC parathyroid to decrease PTH secretion (By similarity). Regulator of
CC vitamin-D metabolism. Negatively regulates osteoblast differentiation
CC and matrix mineralization. {ECO:0000250, ECO:0000269|PubMed:11062477,
CC ECO:0000269|PubMed:11409890, ECO:0000269|PubMed:15040831,
CC ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:18282132}.
CC -!- SUBUNIT: Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between
CC fibroblast growth factors (FGFs) and their receptors is increased by KL
CC and heparan sulfate glycosaminoglycans that function as coreceptors (By
CC similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q9GZV9; P11362: FGFR1; NbExp=2; IntAct=EBI-6594125, EBI-1028277;
CC Q9GZV9; O35082: Kl; Xeno; NbExp=5; IntAct=EBI-6594125, EBI-1570828;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16638743}.
CC Note=Secretion is dependent on O-glycosylation.
CC -!- TISSUE SPECIFICITY: Expressed in osteogenic cells particularly during
CC phases of active bone remodeling. In adult trabecular bone, expressed
CC in osteocytes and flattened bone-lining cells (inactive osteoblasts).
CC {ECO:0000269|PubMed:12952917}.
CC -!- PTM: Following secretion this protein is inactivated by cleavage into a
CC N-terminal fragment and a C-terminal fragment. The processing is
CC effected by proprotein convertases.
CC -!- PTM: O-glycosylated by GALT3. Glycosylation is necessary for secretion;
CC it blocks processing by proprotein convertases when the O-glycan is
CC alpha 2,6-sialylated. Competition between proprotein convertase
CC cleavage and block of cleavage by O-glycosylation determines the level
CC of secreted active FGF23. {ECO:0000269|PubMed:16638743}.
CC -!- DISEASE: Hypophosphatemic rickets, autosomal dominant (ADHR)
CC [MIM:193100]: A disease characterized by isolated renal phosphate
CC wasting, hypophosphatemia, and inappropriately normal 1,25-
CC dihydroxyvitamin D3 (calcitriol) levels. Patients frequently present
CC with bone pain, rickets, and tooth abscesses.
CC {ECO:0000269|PubMed:11062477, ECO:0000269|PubMed:11409890,
CC ECO:0000269|PubMed:16638743}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Tumoral calcinosis, hyperphosphatemic, familial, 2 (HFTC2)
CC [MIM:617993]: 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:15590700, ECO:0000269|PubMed:16030159,
CC ECO:0000269|PubMed:16151858, ECO:0000269|PubMed:24680727}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/fgf23/";
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DR EMBL; AB037973; BAB13477.1; -; mRNA.
DR EMBL; AF263537; AAG09917.1; -; mRNA.
DR EMBL; AB047858; BAB55889.1; -; mRNA.
DR EMBL; AY358323; AAQ88689.1; -; mRNA.
DR EMBL; AY566236; AAS59157.1; -; Genomic_DNA.
DR EMBL; BC069333; AAH69333.1; -; mRNA.
DR EMBL; BC096713; AAH96713.1; -; mRNA.
DR EMBL; BC098147; AAH98147.1; -; mRNA.
DR EMBL; BC098252; AAH98252.1; -; mRNA.
DR CCDS; CCDS8526.1; -.
DR RefSeq; NP_065689.1; NM_020638.2.
DR PDB; 2P39; X-ray; 1.50 A; A=25-179.
DR PDB; 5W21; X-ray; 3.00 A; B=25-204.
DR PDB; 6S22; X-ray; 1.96 A; F=170-181.
DR PDBsum; 2P39; -.
DR PDBsum; 5W21; -.
DR PDBsum; 6S22; -.
DR AlphaFoldDB; Q9GZV9; -.
DR SMR; Q9GZV9; -.
DR BioGRID; 113748; 3.
DR CORUM; Q9GZV9; -.
DR DIP; DIP-58507N; -.
DR IntAct; Q9GZV9; 6.
DR STRING; 9606.ENSP00000237837; -.
DR BindingDB; Q9GZV9; -.
DR ChEMBL; CHEMBL3713913; -.
DR DrugCentral; Q9GZV9; -.
DR TCDB; 1.A.108.1.2; the fibroblast growth factor 2 (fgf2) family.
DR GlyGen; Q9GZV9; 1 site.
DR iPTMnet; Q9GZV9; -.
DR PhosphoSitePlus; Q9GZV9; -.
DR BioMuta; FGF23; -.
DR DMDM; 13626688; -.
DR MassIVE; Q9GZV9; -.
DR PaxDb; Q9GZV9; -.
DR PeptideAtlas; Q9GZV9; -.
DR PRIDE; Q9GZV9; -.
DR ProteomicsDB; 80160; -.
DR ABCD; Q9GZV9; 1 sequenced antibody.
DR Antibodypedia; 22263; 509 antibodies from 36 providers.
DR DNASU; 8074; -.
DR Ensembl; ENST00000237837.2; ENSP00000237837.1; ENSG00000118972.3.
DR GeneID; 8074; -.
DR KEGG; hsa:8074; -.
DR MANE-Select; ENST00000237837.2; ENSP00000237837.1; NM_020638.3; NP_065689.1.
DR UCSC; uc001qmq.1; human.
DR CTD; 8074; -.
DR DisGeNET; 8074; -.
DR GeneCards; FGF23; -.
DR GeneReviews; FGF23; -.
DR HGNC; HGNC:3680; FGF23.
DR HPA; ENSG00000118972; Group enriched (brain, choroid plexus).
DR MalaCards; FGF23; -.
DR MIM; 193100; phenotype.
DR MIM; 605380; gene.
DR MIM; 617993; phenotype.
DR neXtProt; NX_Q9GZV9; -.
DR OpenTargets; ENSG00000118972; -.
DR Orphanet; 89937; Autosomal dominant hypophosphatemic rickets.
DR Orphanet; 306661; Familial hyperphosphatemic tumoral calcinosis/Hyperphosphatemic hyperostosis syndrome.
DR PharmGKB; PA28119; -.
DR VEuPathDB; HostDB:ENSG00000118972; -.
DR eggNOG; KOG3885; Eukaryota.
DR GeneTree; ENSGT00940000160821; -.
DR HOGENOM; CLU_094251_0_0_1; -.
DR InParanoid; Q9GZV9; -.
DR OMA; MHLYTDT; -.
DR OrthoDB; 1345259at2759; -.
DR PhylomeDB; Q9GZV9; -.
DR TreeFam; TF335872; -.
DR PathwayCommons; Q9GZV9; -.
DR Reactome; R-HSA-109704; PI3K Cascade.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-1839122; Signaling by activated point mutants of FGFR1.
DR Reactome; R-HSA-1839130; Signaling by activated point mutants of FGFR3.
DR Reactome; R-HSA-190322; FGFR4 ligand binding and activation.
DR Reactome; R-HSA-190372; FGFR3c ligand binding and activation.
DR Reactome; R-HSA-190373; FGFR1c ligand binding and activation.
DR Reactome; R-HSA-190374; FGFR1c and Klotho ligand binding and activation.
DR Reactome; R-HSA-190375; FGFR2c ligand binding and activation.
DR Reactome; R-HSA-2033519; Activated point mutants of FGFR2.
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-5654219; Phospholipase C-mediated cascade: FGFR1.
DR Reactome; R-HSA-5654221; Phospholipase C-mediated cascade, FGFR2.
DR Reactome; R-HSA-5654227; Phospholipase C-mediated cascade, FGFR3.
DR Reactome; R-HSA-5654228; Phospholipase C-mediated cascade, FGFR4.
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-5654695; PI-3K cascade:FGFR2.
DR Reactome; R-HSA-5654699; SHC-mediated cascade:FGFR2.
DR Reactome; R-HSA-5654700; FRS-mediated FGFR2 signaling.
DR Reactome; R-HSA-5654704; SHC-mediated cascade:FGFR3.
DR Reactome; R-HSA-5654706; FRS-mediated FGFR3 signaling.
DR Reactome; R-HSA-5654710; PI-3K cascade:FGFR3.
DR Reactome; R-HSA-5654712; FRS-mediated FGFR4 signaling.
DR Reactome; R-HSA-5654719; SHC-mediated cascade:FGFR4.
DR Reactome; R-HSA-5654720; PI-3K cascade:FGFR4.
DR Reactome; R-HSA-5654726; Negative regulation of FGFR1 signaling.
DR Reactome; R-HSA-5654727; Negative regulation of FGFR2 signaling.
DR Reactome; R-HSA-5654732; Negative regulation of FGFR3 signaling.
DR Reactome; R-HSA-5654733; Negative regulation of FGFR4 signaling.
DR Reactome; R-HSA-5655253; Signaling by FGFR2 in disease.
DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease.
DR Reactome; R-HSA-5655332; Signaling by FGFR3 in disease.
DR Reactome; R-HSA-5658623; FGFRL1 modulation 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 Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR SignaLink; Q9GZV9; -.
DR SIGNOR; Q9GZV9; -.
DR BioGRID-ORCS; 8074; 6 hits in 1072 CRISPR screens.
DR EvolutionaryTrace; Q9GZV9; -.
DR GeneWiki; Fibroblast_growth_factor_23; -.
DR GenomeRNAi; 8074; -.
DR Pharos; Q9GZV9; Tclin.
DR PRO; PR:Q9GZV9; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9GZV9; protein.
DR Bgee; ENSG00000118972; Expressed in sural nerve and 33 other tissues.
DR Genevisible; Q9GZV9; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0005104; F:fibroblast growth factor receptor binding; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
DR GO; GO:0005105; F:type 1 fibroblast growth factor receptor binding; IBA:GO_Central.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0055074; P:calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0030643; P:cellular phosphate ion homeostasis; IEA:Ensembl.
DR GO; GO:0071354; P:cellular response to interleukin-6; IEA:Ensembl.
DR GO; GO:0044320; P:cellular response to leptin stimulus; IEA:Ensembl.
DR GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEA:Ensembl.
DR GO; GO:0071305; P:cellular response to vitamin D; IEA:Ensembl.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0030502; P:negative regulation of bone mineralization; IDA:UniProtKB.
DR GO; GO:0046888; P:negative regulation of hormone secretion; ISS:UniProtKB.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IDA:UniProtKB.
DR GO; GO:0055062; P:phosphate ion homeostasis; IMP:UniProtKB.
DR GO; GO:0006796; P:phosphate-containing compound metabolic process; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IBA:GO_Central.
DR GO; GO:0090080; P:positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0010980; P:positive regulation of vitamin D 24-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; IBA:GO_Central.
DR GO; GO:0010966; P:regulation of phosphate transport; IDA:UniProtKB.
DR GO; GO:0032026; P:response to magnesium ion; IEA:Ensembl.
DR GO; GO:1904383; P:response to sodium phosphate; IEA:Ensembl.
DR GO; GO:0042369; P:vitamin D catabolic process; IDA:UniProtKB.
DR CDD; cd00058; FGF; 1.
DR InterPro; IPR028304; FGF23.
DR InterPro; IPR002209; Fibroblast_GF_fam.
DR InterPro; IPR008996; IL1/FGF.
DR PANTHER; PTHR11486; PTHR11486; 1.
DR PANTHER; PTHR11486:SF69; PTHR11486:SF69; 1.
DR Pfam; PF00167; FGF; 1.
DR SMART; SM00442; FGF; 1.
DR SUPFAM; SSF50353; SSF50353; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Differentiation; Direct protein sequencing; Disease variant;
KW Disulfide bond; Glycoprotein; Growth factor; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 25..251
FT /note="Fibroblast growth factor 23"
FT /id="PRO_0000008998"
FT CHAIN 25..179
FT /note="Fibroblast growth factor 23 N-terminal peptide"
FT /id="PRO_0000352875"
FT CHAIN 180..251
FT /note="Fibroblast growth factor 23 C-terminal peptide"
FT /id="PRO_0000352876"
FT REGION 172..221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 175..193
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 179..180
FT /note="Cleavage; by proprotein convertases"
FT CARBOHYD 178
FT /note="O-linked (GalNAc) threonine"
FT /evidence="ECO:0000269|PubMed:16638743"
FT DISULFID 95..113
FT VARIANT 71
FT /note="S -> G (in HFTC2; only the C-terminal fragment is
FT secreted, whereas the intact protein is retained in the
FT Golgi complex; dbSNP:rs104894342)"
FT /evidence="ECO:0000269|PubMed:15590700"
FT /id="VAR_023831"
FT VARIANT 96
FT /note="M -> T (in HFTC2; dbSNP:rs104894343)"
FT /evidence="ECO:0000269|PubMed:16151858"
FT /id="VAR_071711"
FT VARIANT 129
FT /note="S -> F (in HFTC2; full-length and N-terminal
FT fragments are barely detectable, whereas a C-terminal
FT fragment with the same molecular weight as that from wild-
FT type can be detected; dbSNP:rs104894344)"
FT /evidence="ECO:0000269|PubMed:16030159"
FT /id="VAR_071712"
FT VARIANT 157
FT /note="F -> L (in HFTC2; dbSNP:rs772964687)"
FT /evidence="ECO:0000269|PubMed:24680727"
FT /id="VAR_071713"
FT VARIANT 176
FT /note="R -> Q (in ADHR; partially resistant to cleavage by
FT furin; dbSNP:rs104894347)"
FT /evidence="ECO:0000269|PubMed:11062477,
FT ECO:0000269|PubMed:16638743"
FT /id="VAR_010717"
FT VARIANT 179
FT /note="R -> Q (in ADHR; C-terminal processing is abolished;
FT reduced proteolysis by PHEX; resistant to cleavage by
FT furin; dbSNP:rs193922702)"
FT /evidence="ECO:0000269|PubMed:11062477,
FT ECO:0000269|PubMed:11409890, ECO:0000269|PubMed:16638743"
FT /id="VAR_010719"
FT VARIANT 179
FT /note="R -> W (in ADHR; C-terminal processing is abolished;
FT dbSNP:rs28937882)"
FT /evidence="ECO:0000269|PubMed:11062477"
FT /id="VAR_010718"
FT VARIANT 195
FT /note="P -> S (in dbSNP:rs13312793)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_018887"
FT VARIANT 239
FT /note="T -> M (in dbSNP:rs7955866)"
FT /evidence="ECO:0000269|PubMed:11062477, ECO:0000269|Ref.5"
FT /id="VAR_010720"
FT STRAND 32..36
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:2P39"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:2P39"
FT STRAND 52..55
FT /evidence="ECO:0007829|PDB:2P39"
FT STRAND 61..66
FT /evidence="ECO:0007829|PDB:2P39"
FT TURN 69..71
FT /evidence="ECO:0007829|PDB:2P39"
FT STRAND 73..77
FT /evidence="ECO:0007829|PDB:2P39"
FT HELIX 79..81
FT /evidence="ECO:0007829|PDB:2P39"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:2P39"
FT TURN 88..91
FT /evidence="ECO:0007829|PDB:2P39"
FT STRAND 92..96
FT /evidence="ECO:0007829|PDB:2P39"
FT STRAND 102..107
FT /evidence="ECO:0007829|PDB:2P39"
FT TURN 110..112
FT /evidence="ECO:0007829|PDB:2P39"
FT STRAND 115..119
FT /evidence="ECO:0007829|PDB:2P39"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 125..128
FT /evidence="ECO:0007829|PDB:2P39"
FT TURN 130..132
FT /evidence="ECO:0007829|PDB:2P39"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:2P39"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:5W21"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:2P39"
FT STRAND 157..161
FT /evidence="ECO:0007829|PDB:2P39"
FT HELIX 166..168
FT /evidence="ECO:0007829|PDB:2P39"
SQ SEQUENCE 251 AA; 27954 MW; 6093BD0CC50C2489 CRC64;
MLGARLRLWV CALCSVCSMS VLRAYPNASP LLGSSWGGLI HLYTATARNS YHLQIHKNGH
VDGAPHQTIY SALMIRSEDA GFVVITGVMS RRYLCMDFRG NIFGSHYFDP ENCRFQHQTL
ENGYDVYHSP QYHFLVSLGR AKRAFLPGMN PPPYSQFLSR RNEIPLIHFN TPIPRRHTRS
AEDDSERDPL NVLKPRARMT PAPASCSQEL PSAEDNSPMA SDPLGVVRGG RVNTHAGGTG
PEGCRPFAKF I
