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 24-JAN-2024, entry version 215. 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/jci18399; 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. 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 GLYCOSYLATION AT THR-171 AND THR-178, PHOSPHORYLATION AT SER-180, AND RP MUTAGENESIS OF THR-178. RX PubMed=31932717; DOI=10.1038/s41589-019-0444-x; RA de Las Rivas M., Paul Daniel E.J., Narimatsu Y., Companon I., Kato K., RA Hermosilla P., Thureau A., Ceballos-Laita L., Coelho H., Bernado P., RA Marcelo F., Hansen L., Maeda R., Lostao A., Corzana F., Clausen H., RA Gerken T.A., Hurtado-Guerrero R.; RT "Molecular basis for fibroblast growth factor 23 O-glycosylation by GalNAc- RT T3."; RL Nat. Chem. Biol. 16:351-360(2020). RN [19] 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 [20] 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 [21] 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 [22] 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 [23] 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 (PubMed:11062477). CC Inhibits renal tubular phosphate transport by reducing SLC34A1 levels CC (PubMed:11409890). Up-regulates EGR1 expression in the presence of KL CC (By similarity). Acts directly on the parathyroid to decrease PTH CC secretion (By similarity). Regulator of vitamin-D metabolism CC (PubMed:15040831). Negatively regulates osteoblast differentiation and CC matrix mineralization (PubMed:18282132). {ECO:0000250|UniProtKB:Q8VI82, CC ECO:0000269|PubMed:11062477, ECO:0000269|PubMed:11409890, CC ECO:0000269|PubMed:15040831, ECO:0000269|PubMed:16597617, CC ECO:0000269|PubMed:18282132}. CC -!- SUBUNIT: Interacts with FGFR1, FGFR2, FGFR3 and FGFR4 CC (PubMed:16597617). Affinity between fibroblast growth factors (FGFs) CC and their receptors is increased by KL and heparan sulfate CC glycosaminoglycans that function as coreceptors (By similarity). CC {ECO:0000250|UniProtKB:Q9EPC2, ECO:0000269|PubMed:16597617}. 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. {ECO:0000269|PubMed:11157998, CC ECO:0000269|PubMed:12130585, ECO:0000269|PubMed:15268897}. CC -!- PTM: O-glycosylated at Thr-171 and Thr-178 by GALNT3 and glycosylation CC of Thr-178 requires previous glycosylation at Thr171. Glycosylation is CC necessary for secretion; it blocks processing by proprotein convertases CC when the O-glycan is alpha 2,6-sialylated. Competition between CC proprotein convertase cleavage and block of cleavage by O-glycosylation CC determines the level of secreted active FGF23. CC {ECO:0000269|PubMed:16638743, ECO:0000269|PubMed:31932717}. CC -!- PTM: Phosphorylation at Ser-180 mediated by FAM20C slows down CC glycosylation at Thr-178 notably. {ECO:0000269|PubMed:31932717}. 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/"; 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; 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 PDB; 7YSH; EM; 2.74 A; B=25-251. DR PDB; 7YSU; EM; 3.20 A; B=25-203. DR PDB; 7YSW; EM; 3.03 A; B=25-203. DR PDBsum; 2P39; -. DR PDBsum; 5W21; -. DR PDBsum; 6S22; -. DR PDBsum; 7YSH; -. DR PDBsum; 7YSU; -. DR PDBsum; 7YSW; -. DR AlphaFoldDB; Q9GZV9; -. DR EMDB; EMD-34082; -. DR EMDB; EMD-34084; -. 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 GlyCosmos; Q9GZV9; 1 site, No reported glycans. DR GlyGen; Q9GZV9; 2 sites. DR iPTMnet; Q9GZV9; -. DR PhosphoSitePlus; Q9GZV9; -. DR BioMuta; FGF23; -. DR DMDM; 13626688; -. DR MassIVE; Q9GZV9; -. DR PaxDb; 9606-ENSP00000237837; -. DR PeptideAtlas; Q9GZV9; -. DR ABCD; Q9GZV9; 1 sequenced antibody. DR Antibodypedia; 22263; 597 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 AGR; HGNC:3680; -. DR CTD; 8074; -. DR DisGeNET; 8074; -. DR GeneCards; FGF23; -. DR GeneReviews; FGF23; -. DR HGNC; HGNC:3680; FGF23. DR HPA; ENSG00000118972; Tissue enhanced (heart muscle, liver). 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; FRFNTPE; -. DR OrthoDB; 3833523at2759; -. 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; 7 hits in 1156 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 30 other cell types or tissues. 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: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: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:0030643; P:intracellular phosphate ion homeostasis; IEA:Ensembl. 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:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IEA:Ensembl. 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: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 Gene3D; 2.80.10.50; -; 1. DR InterPro; IPR002209; Fibroblast_GF_fam. DR InterPro; IPR008996; IL1/FGF. DR PANTHER; PTHR11486; FIBROBLAST GROWTH FACTOR; 1. DR PANTHER; PTHR11486:SF69; FIBROBLAST GROWTH FACTOR 23; 1. DR Pfam; PF00167; FGF; 1. DR PRINTS; PR00262; IL1HBGF. DR SMART; SM00442; FGF; 1. DR SUPFAM; SSF50353; Cytokine; 1. DR Genevisible; Q9GZV9; HS. PE 1: Evidence at protein level; KW 3D-structure; Differentiation; Direct protein sequencing; Disease variant; KW Disulfide bond; Glycoprotein; Growth factor; Phosphoprotein; KW Reference proteome; Secreted; 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 MOD_RES 180 FT /note="Phosphoserine; by FAM20C" FT /evidence="ECO:0000269|PubMed:31932717" FT CARBOHYD 171 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:31932717" FT CARBOHYD 178 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:16638743, FT ECO:0000269|PubMed:31932717" 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 FT wild-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 MUTAGEN 178 FT /note="T->A: Loss of glycosylation." FT /evidence="ECO:0000269|PubMed:31932717" FT STRAND 32..34 FT /evidence="ECO:0007829|PDB:7YSH" FT STRAND 36..38 FT /evidence="ECO:0007829|PDB:7YSW" 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 //