ID   FGF23_RAT               Reviewed;         251 AA.
AC   Q8VI82;
DT   01-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2002, sequence version 1.
DT   24-JAN-2024, entry version 135.
DE   RecName: Full=Fibroblast growth factor 23;
DE            Short=FGF-23;
DE   Flags: Precursor;
GN   Name=Fgf23;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Itoh N.;
RT   "Rattus norvegicus fgf23.";
RL   Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION.
RX   PubMed=17086194; DOI=10.1038/nature05315;
RA   Urakawa I., Yamazaki Y., Shimada T., Iijima K., Hasegawa H., Okawa K.,
RA   Fujita T., Fukumoto S., Yamashita T.;
RT   "Klotho converts canonical FGF receptor into a specific receptor for
RT   FGF23.";
RL   Nature 444:770-774(2006).
RN   [3]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=17992255; DOI=10.1172/jci32409;
RA   Ben-Dov I.Z., Galitzer H., Lavi-Moshayoff V., Goetz R., Kuro-o M.,
RA   Mohammadi M., Sirkis R., Naveh-Many T., Silver J.;
RT   "The parathyroid is a target organ for FGF23 in rats.";
RL   J. Clin. Invest. 117:4003-4008(2007).
CC   -!- FUNCTION: Regulator of phosphate homeostasis (By similarity). Inhibits
CC       renal tubular phosphate transport by reducing SLC34A1 levels (By
CC       similarity). Regulator of vitamin-D metabolism (By similarity).
CC       Negatively regulates osteoblasts differentiation and matrix
CC       mineralization (By similarity). Acts directly on the parathyroid to
CC       decrease PTH secretion (PubMed:17992255). Up-regulates EGR1 expression
CC       in the presence of KL (PubMed:17086194). {ECO:0000250|UniProtKB:Q9GZV9,
CC       ECO:0000269|PubMed:17086194, ECO:0000269|PubMed:17992255}.
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|UniProtKB:Q9EPC2,
CC       ECO:0000250|UniProtKB:Q9GZV9}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9GZV9}.
CC       Note=Secretion is dependent on O-glycosylation.
CC       {ECO:0000250|UniProtKB:Q9GZV9}.
CC   -!- TISSUE SPECIFICITY: Expressed in the parathyroid.
CC       {ECO:0000269|PubMed:17992255}.
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 (By similarity).
CC       {ECO:0000250|UniProtKB:Q9GZV9}.
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 (By similarity).
CC       {ECO:0000250|UniProtKB:Q9GZV9}.
CC   -!- PTM: Phosphorylation at Ser-180 mediated by FAM20C slows down
CC       glycosylation at Thr-178 notably. {ECO:0000250|UniProtKB:Q9GZV9}.
CC   -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
CC       {ECO:0000305}.
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DR   EMBL; AB078777; BAB84108.1; -; mRNA.
DR   RefSeq; NP_570110.1; NM_130754.1.
DR   AlphaFoldDB; Q8VI82; -.
DR   SMR; Q8VI82; -.
DR   STRING; 10116.ENSRNOP00000075536; -.
DR   GlyCosmos; Q8VI82; 1 site, No reported glycans.
DR   GlyGen; Q8VI82; 2 sites.
DR   PhosphoSitePlus; Q8VI82; -.
DR   PaxDb; 10116-ENSRNOP00000026888; -.
DR   Ensembl; ENSRNOT00000107111.1; ENSRNOP00000087703.1; ENSRNOG00000066556.1.
DR   Ensembl; ENSRNOT00055018109; ENSRNOP00055014551; ENSRNOG00055010713.
DR   Ensembl; ENSRNOT00060030149; ENSRNOP00060024337; ENSRNOG00060017634.
DR   Ensembl; ENSRNOT00065057716; ENSRNOP00065047503; ENSRNOG00065033593.
DR   GeneID; 170583; -.
DR   KEGG; rno:170583; -.
DR   UCSC; RGD:620178; rat.
DR   AGR; RGD:620178; -.
DR   CTD; 8074; -.
DR   RGD; 620178; Fgf23.
DR   eggNOG; KOG3885; Eukaryota.
DR   GeneTree; ENSGT00940000160821; -.
DR   HOGENOM; CLU_094251_0_0_1; -.
DR   InParanoid; Q8VI82; -.
DR   OMA; FRFNTPE; -.
DR   OrthoDB; 3833523at2759; -.
DR   PhylomeDB; Q8VI82; -.
DR   TreeFam; TF335872; -.
DR   Reactome; R-RNO-109704; PI3K Cascade.
DR   Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
DR   Reactome; R-RNO-190322; FGFR4 ligand binding and activation.
DR   Reactome; R-RNO-190372; FGFR3c ligand binding and activation.
DR   Reactome; R-RNO-190373; FGFR1c ligand binding and activation.
DR   Reactome; R-RNO-190374; FGFR1c and Klotho ligand binding and activation.
DR   Reactome; R-RNO-190375; FGFR2c ligand binding and activation.
DR   Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Reactome; R-RNO-5654219; Phospholipase C-mediated cascade: FGFR1.
DR   Reactome; R-RNO-5654221; Phospholipase C-mediated cascade, FGFR2.
DR   Reactome; R-RNO-5654227; Phospholipase C-mediated cascade, FGFR3.
DR   Reactome; R-RNO-5654228; Phospholipase C-mediated cascade, FGFR4.
DR   Reactome; R-RNO-5654687; Downstream signaling of activated FGFR1.
DR   Reactome; R-RNO-5654688; SHC-mediated cascade:FGFR1.
DR   Reactome; R-RNO-5654689; PI-3K cascade:FGFR1.
DR   Reactome; R-RNO-5654693; FRS-mediated FGFR1 signaling.
DR   Reactome; R-RNO-5654695; PI-3K cascade:FGFR2.
DR   Reactome; R-RNO-5654699; SHC-mediated cascade:FGFR2.
DR   Reactome; R-RNO-5654700; FRS-mediated FGFR2 signaling.
DR   Reactome; R-RNO-5654704; SHC-mediated cascade:FGFR3.
DR   Reactome; R-RNO-5654706; FRS-mediated FGFR3 signaling.
DR   Reactome; R-RNO-5654710; PI-3K cascade:FGFR3.
DR   Reactome; R-RNO-5654712; FRS-mediated FGFR4 signaling.
DR   Reactome; R-RNO-5654719; SHC-mediated cascade:FGFR4.
DR   Reactome; R-RNO-5654720; PI-3K cascade:FGFR4.
DR   Reactome; R-RNO-5654726; Negative regulation of FGFR1 signaling.
DR   Reactome; R-RNO-5654727; Negative regulation of FGFR2 signaling.
DR   Reactome; R-RNO-5654732; Negative regulation of FGFR3 signaling.
DR   Reactome; R-RNO-5654733; Negative regulation of FGFR4 signaling.
DR   Reactome; R-RNO-5658623; FGFRL1 modulation of FGFR1 signaling.
DR   Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR   PRO; PR:Q8VI82; -.
DR   Proteomes; UP000002494; Chromosome 4.
DR   Bgee; ENSRNOG00000052205; Expressed in thymus and 3 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005615; C:extracellular space; IDA:RGD.
DR   GO; GO:0005104; F:fibroblast growth factor receptor binding; ISO:RGD.
DR   GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
DR   GO; GO:0005105; F:type 1 fibroblast growth factor receptor binding; ISO:RGD.
DR   GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR   GO; GO:0055074; P:calcium ion homeostasis; ISO:RGD.
DR   GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR   GO; GO:0071354; P:cellular response to interleukin-6; IEP:RGD.
DR   GO; GO:0044320; P:cellular response to leptin stimulus; IEP:RGD.
DR   GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEP:RGD.
DR   GO; GO:0071305; P:cellular response to vitamin D; IEP:RGD.
DR   GO; GO:0070371; P:ERK1 and ERK2 cascade; ISO:RGD.
DR   GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; ISO:RGD.
DR   GO; GO:0030643; P:intracellular phosphate ion homeostasis; ISO:RGD.
DR   GO; GO:0000165; P:MAPK cascade; ISO:RGD.
DR   GO; GO:0030502; P:negative regulation of bone mineralization; ISO:RGD.
DR   GO; GO:0046888; P:negative regulation of hormone secretion; IDA:UniProtKB.
DR   GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISO:RGD.
DR   GO; GO:0055062; P:phosphate ion homeostasis; ISO:RGD.
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; ISO:RGD.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
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; ISO:RGD.
DR   GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
DR   GO; GO:0030500; P:regulation of bone mineralization; ISO:RGD.
DR   GO; GO:0030334; P:regulation of cell migration; IBA:GO_Central.
DR   GO; GO:0010966; P:regulation of phosphate transport; ISO:RGD.
DR   GO; GO:0032026; P:response to magnesium ion; IEP:RGD.
DR   GO; GO:1904383; P:response to sodium phosphate; IEP:RGD.
DR   GO; GO:0042369; P:vitamin D catabolic process; ISO:RGD.
DR   GO; GO:0042359; P:vitamin D metabolic process; IEP:RGD.
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   SMART; SM00442; FGF; 1.
DR   SUPFAM; SSF50353; Cytokine; 1.
DR   PROSITE; PS00247; HBGF_FGF; 1.
DR   Genevisible; Q8VI82; RN.
PE   2: Evidence at transcript level;
KW   Differentiation; Disulfide bond; Glycoprotein; Growth factor;
KW   Phosphoprotein; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   CHAIN           25..251
FT                   /note="Fibroblast growth factor 23"
FT                   /id="PRO_0000009000"
FT   REGION          175..251
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   COMPBIAS        228..242
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         180
FT                   /note="Phosphoserine; by FAM20C"
FT                   /evidence="ECO:0000250|UniProtKB:Q9GZV9"
FT   CARBOHYD        171
FT                   /note="O-linked (GalNAc) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9GZV9"
FT   CARBOHYD        178
FT                   /note="O-linked (GalNAc) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9GZV9"
FT   DISULFID        95..113
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   251 AA;  27912 MW;  35A229E1B3900593 CRC64;
     MLGACLRLLV GALCTVCSLG TARAYSDTSP LLGSNWGSLT HLYTATARNS YHLQIHRDGH
     VDGTPHQTIY SALMITSEDA GSVVIIGAMT RRFLCMDLRG NIFGSYHFSP ENCRFRQWTL
     ENGYDVYLSP KHHYLVSLGR SKRIFQPGTN PPPFSQFLAR RNEVPLLHFY TARPRRHTRS
     AEDPPERDPL NVLKPRPRAT PIPVSCSREL PSAEEGGPAA SDPLGVLRRG RGDARRGAGG
     TDRCRPFPRF V
//