FGF23_RAT
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 03-AUG-2022, entry version 127.
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. Up-regulates EGR1 expression in the presence of
CC KL. {ECO:0000250, ECO:0000269|PubMed:17086194,
CC 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}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. Note=Secretion is
CC dependent on O-glycosylation. {ECO:0000250}.
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). {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
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.ENSRNOP00000026888; -.
DR GlyGen; Q8VI82; 1 site.
DR PaxDb; Q8VI82; -.
DR Ensembl; ENSRNOT00000107111; ENSRNOP00000087703; ENSRNOG00000066556.
DR GeneID; 170583; -.
DR KEGG; rno:170583; -.
DR UCSC; RGD:620178; rat.
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; MHLYTDT; -.
DR OrthoDB; 1345259at2759; -.
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 tissues.
DR Genevisible; Q8VI82; RN.
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:0030643; P:cellular phosphate ion homeostasis; ISO:RGD.
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: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:0006796; P:phosphate-containing compound metabolic process; IEP:RGD.
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; 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:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0010980; P:positive regulation of vitamin D 24-hydroxylase activity; ISO:RGD.
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 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.
DR PROSITE; PS00247; HBGF_FGF; 1.
PE 2: Evidence at transcript level;
KW Differentiation; Disulfide bond; Glycoprotein; Growth factor;
KW 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 CARBOHYD 178
FT /note="O-linked (GalNAc) threonine"
FT /evidence="ECO:0000250"
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
