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Protein

Fibroblast growth factor 23

Gene

FGF23

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Regulator of phosphate homeostasis. Inhibits renal tubular phosphate transport by reducing SLC34A1 levels. Upregulates EGR1 expression in the presence of KL (By similarity). Acts directly on the parathyroid to decrease PTH secretion (By similarity). Regulator of vitamin-D metabolism. Negatively regulates osteoblast differentiation and matrix mineralization.By similarity5 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Keywords - Biological processi

Differentiation

Enzyme and pathway databases

BioCyciZFISH:ENSG00000118972-MONOMER.
ReactomeiR-HSA-109704. PI3K Cascade.
R-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1839122. Signaling by activated point mutants of FGFR1.
R-HSA-1839130. Signaling by activated point mutants of FGFR3.
R-HSA-190322. FGFR4 ligand binding and activation.
R-HSA-190372. FGFR3c ligand binding and activation.
R-HSA-190373. FGFR1c ligand binding and activation.
R-HSA-190374. FGFR1c and Klotho ligand binding and activation.
R-HSA-190375. FGFR2c ligand binding and activation.
R-HSA-2033514. FGFR3 mutant receptor activation.
R-HSA-2033519. Activated point mutants of FGFR2.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-5654219. Phospholipase C-mediated cascade: FGFR1.
R-HSA-5654221. Phospholipase C-mediated cascade, FGFR2.
R-HSA-5654227. Phospholipase C-mediated cascade, FGFR3.
R-HSA-5654228. Phospholipase C-mediated cascade, FGFR4.
R-HSA-5654687. Downstream signaling of activated FGFR1.
R-HSA-5654688. SHC-mediated cascade:FGFR1.
R-HSA-5654689. PI-3K cascade:FGFR1.
R-HSA-5654693. FRS-mediated FGFR1 signaling.
R-HSA-5654695. PI-3K cascade:FGFR2.
R-HSA-5654699. SHC-mediated cascade:FGFR2.
R-HSA-5654700. FRS-mediated FGFR2 signaling.
R-HSA-5654704. SHC-mediated cascade:FGFR3.
R-HSA-5654706. FRS-mediated FGFR3 signaling.
R-HSA-5654710. PI-3K cascade:FGFR3.
R-HSA-5654712. FRS-mediated FGFR4 signaling.
R-HSA-5654719. SHC-mediated cascade:FGFR4.
R-HSA-5654720. PI-3K cascade:FGFR4.
R-HSA-5654726. Negative regulation of FGFR1 signaling.
R-HSA-5654727. Negative regulation of FGFR2 signaling.
R-HSA-5654732. Negative regulation of FGFR3 signaling.
R-HSA-5654733. Negative regulation of FGFR4 signaling.
R-HSA-5655253. Signaling by FGFR2 in disease.
R-HSA-5655302. Signaling by FGFR1 in disease.
R-HSA-5658623. FGFRL1 modulation of FGFR1 signaling.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-HSA-8853338. Signaling by FGFR3 point mutants in cancer.
SIGNORiQ9GZV9.

Names & Taxonomyi

Protein namesi
Recommended name:
Fibroblast growth factor 23
Short name:
FGF-23
Alternative name(s):
Phosphatonin
Tumor-derived hypophosphatemia-inducing factor
Cleaved into the following 2 chains:
Gene namesi
Name:FGF23
Synonyms:HYPF
ORF Names:UNQ3027/PRO9828
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:3680. FGF23.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: Reactome
  • extracellular space Source: UniProtKB
  • Golgi lumen Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Hypophosphatemic rickets, autosomal dominant (ADHR)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by isolated renal phosphate wasting, hypophosphatemia, and inappropriately normal 1,25-dihydroxyvitamin D3 (calcitriol) levels. Patients frequently present with bone pain, rickets, and tooth abscesses.
See also OMIM:193100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_010717176R → Q in ADHR; partially resistant to cleavage by furin. 2 PublicationsCorresponds to variant rs104894347dbSNPEnsembl.1
Natural variantiVAR_010719179R → Q in ADHR; C-terminal processing is abolished; reduced proteolysis by PHEX; resistant to cleavage by furin. 3 PublicationsCorresponds to variant rs193922702dbSNPEnsembl.1
Natural variantiVAR_010718179R → W in ADHR; C-terminal processing is abolished. 1 PublicationCorresponds to variant rs28937882dbSNPEnsembl.1
Tumoral calcinosis, hyperphosphatemic, familial (HFTC)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA severe metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues. Some patients manifest recurrent, transient, painful swellings of the long bones associated with the radiographic findings of periosteal reaction and cortical hyperostosis and absence of skin involvement.
See also OMIM:211900
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02383171S → G in HFTC; only the C-terminal fragment is secreted, whereas the intact protein is retained in the Golgi complex. 1 PublicationCorresponds to variant rs104894342dbSNPEnsembl.1
Natural variantiVAR_07171196M → T in HFTC. 1 PublicationCorresponds to variant rs104894343dbSNPEnsembl.1
Natural variantiVAR_071712129S → F in HFTC; full-length and N-terminal fragments are barely detectable, whereas a C-terminal fragment with the same molecular weight as that from wild-type can be detected. 1 PublicationCorresponds to variant rs104894344dbSNPEnsembl.1
Natural variantiVAR_071713157F → L in HFTC. 1 PublicationCorresponds to variant rs772964687dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi8074.
MalaCardsiFGF23.
MIMi193100. phenotype.
211900. phenotype.
OpenTargetsiENSG00000118972.
Orphaneti89937. Autosomal dominant hypophosphatemic rickets.
306661. Familial tumoral calcinosis.
PharmGKBiPA28119.

Polymorphism and mutation databases

BioMutaiFGF23.
DMDMi13626688.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 241 PublicationAdd BLAST24
ChainiPRO_000000899825 – 251Fibroblast growth factor 23Add BLAST227
ChainiPRO_000035287525 – 179Fibroblast growth factor 23 N-terminal peptideAdd BLAST155
ChainiPRO_0000352876180 – 251Fibroblast growth factor 23 C-terminal peptideAdd BLAST72

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi95 ↔ 113
Glycosylationi178O-linked (GalNAc)1 Publication1

Post-translational modificationi

Following secretion this protein is inactivated by cleavage into a N-terminal fragment and a C-terminal fragment. The processing is effected by proprotein convertases.
O-glycosylated by GALT3. Glycosylation is necessary for secretion; it blocks processing by proprotein convertases when the O-glycan is alpha 2,6-sialylated. Competition between proprotein convertase cleavage and block of cleavage by O-glycosylation determines the level of secreted active FGF23.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei179 – 180Cleavage; by proprotein convertases2

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9GZV9.
PeptideAtlasiQ9GZV9.
PRIDEiQ9GZV9.

PTM databases

iPTMnetiQ9GZV9.
PhosphoSitePlusiQ9GZV9.

Expressioni

Tissue specificityi

Expressed in osteogenic cells particularly during phases of active bone remodeling. In adult trabecular bone, expressed in osteocytes and flattened bone-lining cells (inactive osteoblasts).1 Publication

Gene expression databases

BgeeiENSG00000118972.
CleanExiHS_FGF23.
GenevisibleiQ9GZV9. HS.

Interactioni

Subunit structurei

Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by KL and heparan sulfate glycosaminoglycans that function as coreceptors (By similarity).By similarity

Protein-protein interaction databases

BioGridi113748. 2 interactors.
DIPiDIP-58507N.
IntActiQ9GZV9. 1 interactor.
STRINGi9606.ENSP00000237837.

Structurei

Secondary structure

1251
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi40 – 43Combined sources4
Beta strandi47 – 49Combined sources3
Beta strandi52 – 55Combined sources4
Beta strandi61 – 66Combined sources6
Turni69 – 71Combined sources3
Beta strandi73 – 77Combined sources5
Helixi79 – 81Combined sources3
Beta strandi82 – 87Combined sources6
Turni88 – 91Combined sources4
Beta strandi92 – 96Combined sources5
Beta strandi102 – 107Combined sources6
Turni110 – 112Combined sources3
Beta strandi115 – 119Combined sources5
Beta strandi125 – 128Combined sources4
Turni130 – 132Combined sources3
Beta strandi138 – 140Combined sources3
Helixi153 – 155Combined sources3
Beta strandi157 – 161Combined sources5
Helixi166 – 168Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2P39X-ray1.50A25-179[»]
ProteinModelPortaliQ9GZV9.
SMRiQ9GZV9.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9GZV9.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3885. Eukaryota.
ENOG4111IPH. LUCA.
GeneTreeiENSGT00530000063469.
HOGENOMiHOG000112573.
HOVERGENiHBG051613.
InParanoidiQ9GZV9.
KOiK04358.
OMAiSWGGLTH.
OrthoDBiEOG091G0NAY.
PhylomeDBiQ9GZV9.
TreeFamiTF335872.

Family and domain databases

CDDicd00058. FGF. 1 hit.
InterProiIPR008996. Cytokine_IL1-like.
IPR028304. FGF23.
IPR002209. Fibroblast_GF_fam.
IPR028142. IL-1_fam/FGF_fam.
[Graphical view]
PANTHERiPTHR11486. PTHR11486. 1 hit.
PTHR11486:SF69. PTHR11486:SF69. 1 hit.
PfamiPF00167. FGF. 1 hit.
[Graphical view]
PRINTSiPR00262. IL1HBGF.
SMARTiSM00442. FGF. 1 hit.
[Graphical view]
SUPFAMiSSF50353. SSF50353. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9GZV9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLGARLRLWV CALCSVCSMS VLRAYPNASP LLGSSWGGLI HLYTATARNS
60 70 80 90 100
YHLQIHKNGH VDGAPHQTIY SALMIRSEDA GFVVITGVMS RRYLCMDFRG
110 120 130 140 150
NIFGSHYFDP ENCRFQHQTL ENGYDVYHSP QYHFLVSLGR AKRAFLPGMN
160 170 180 190 200
PPPYSQFLSR RNEIPLIHFN TPIPRRHTRS AEDDSERDPL NVLKPRARMT
210 220 230 240 250
PAPASCSQEL PSAEDNSPMA SDPLGVVRGG RVNTHAGGTG PEGCRPFAKF

I
Length:251
Mass (Da):27,954
Last modified:March 1, 2001 - v1
Checksum:i6093BD0CC50C2489
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02383171S → G in HFTC; only the C-terminal fragment is secreted, whereas the intact protein is retained in the Golgi complex. 1 PublicationCorresponds to variant rs104894342dbSNPEnsembl.1
Natural variantiVAR_07171196M → T in HFTC. 1 PublicationCorresponds to variant rs104894343dbSNPEnsembl.1
Natural variantiVAR_071712129S → F in HFTC; full-length and N-terminal fragments are barely detectable, whereas a C-terminal fragment with the same molecular weight as that from wild-type can be detected. 1 PublicationCorresponds to variant rs104894344dbSNPEnsembl.1
Natural variantiVAR_071713157F → L in HFTC. 1 PublicationCorresponds to variant rs772964687dbSNPEnsembl.1
Natural variantiVAR_010717176R → Q in ADHR; partially resistant to cleavage by furin. 2 PublicationsCorresponds to variant rs104894347dbSNPEnsembl.1
Natural variantiVAR_010719179R → Q in ADHR; C-terminal processing is abolished; reduced proteolysis by PHEX; resistant to cleavage by furin. 3 PublicationsCorresponds to variant rs193922702dbSNPEnsembl.1
Natural variantiVAR_010718179R → W in ADHR; C-terminal processing is abolished. 1 PublicationCorresponds to variant rs28937882dbSNPEnsembl.1
Natural variantiVAR_018887195P → S.1 PublicationCorresponds to variant rs13312793dbSNPEnsembl.1
Natural variantiVAR_010720239T → M.2 PublicationsCorresponds to variant rs7955866dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB037973 mRNA. Translation: BAB13477.1.
AF263537 mRNA. Translation: AAG09917.1.
AB047858 mRNA. Translation: BAB55889.1.
AY358323 mRNA. Translation: AAQ88689.1.
AY566236 Genomic DNA. Translation: AAS59157.1.
BC069333 mRNA. Translation: AAH69333.1.
BC096713 mRNA. Translation: AAH96713.1.
BC098147 mRNA. Translation: AAH98147.1.
BC098252 mRNA. Translation: AAH98252.1.
CCDSiCCDS8526.1.
RefSeqiNP_065689.1. NM_020638.2.
UniGeneiHs.287370.

Genome annotation databases

EnsembliENST00000237837; ENSP00000237837; ENSG00000118972.
GeneIDi8074.
KEGGihsa:8074.
UCSCiuc001qmq.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB037973 mRNA. Translation: BAB13477.1.
AF263537 mRNA. Translation: AAG09917.1.
AB047858 mRNA. Translation: BAB55889.1.
AY358323 mRNA. Translation: AAQ88689.1.
AY566236 Genomic DNA. Translation: AAS59157.1.
BC069333 mRNA. Translation: AAH69333.1.
BC096713 mRNA. Translation: AAH96713.1.
BC098147 mRNA. Translation: AAH98147.1.
BC098252 mRNA. Translation: AAH98252.1.
CCDSiCCDS8526.1.
RefSeqiNP_065689.1. NM_020638.2.
UniGeneiHs.287370.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2P39X-ray1.50A25-179[»]
ProteinModelPortaliQ9GZV9.
SMRiQ9GZV9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113748. 2 interactors.
DIPiDIP-58507N.
IntActiQ9GZV9. 1 interactor.
STRINGi9606.ENSP00000237837.

PTM databases

iPTMnetiQ9GZV9.
PhosphoSitePlusiQ9GZV9.

Polymorphism and mutation databases

BioMutaiFGF23.
DMDMi13626688.

Proteomic databases

PaxDbiQ9GZV9.
PeptideAtlasiQ9GZV9.
PRIDEiQ9GZV9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000237837; ENSP00000237837; ENSG00000118972.
GeneIDi8074.
KEGGihsa:8074.
UCSCiuc001qmq.1. human.

Organism-specific databases

CTDi8074.
DisGeNETi8074.
GeneCardsiFGF23.
HGNCiHGNC:3680. FGF23.
MalaCardsiFGF23.
MIMi193100. phenotype.
211900. phenotype.
605380. gene.
neXtProtiNX_Q9GZV9.
OpenTargetsiENSG00000118972.
Orphaneti89937. Autosomal dominant hypophosphatemic rickets.
306661. Familial tumoral calcinosis.
PharmGKBiPA28119.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3885. Eukaryota.
ENOG4111IPH. LUCA.
GeneTreeiENSGT00530000063469.
HOGENOMiHOG000112573.
HOVERGENiHBG051613.
InParanoidiQ9GZV9.
KOiK04358.
OMAiSWGGLTH.
OrthoDBiEOG091G0NAY.
PhylomeDBiQ9GZV9.
TreeFamiTF335872.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000118972-MONOMER.
ReactomeiR-HSA-109704. PI3K Cascade.
R-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1839122. Signaling by activated point mutants of FGFR1.
R-HSA-1839130. Signaling by activated point mutants of FGFR3.
R-HSA-190322. FGFR4 ligand binding and activation.
R-HSA-190372. FGFR3c ligand binding and activation.
R-HSA-190373. FGFR1c ligand binding and activation.
R-HSA-190374. FGFR1c and Klotho ligand binding and activation.
R-HSA-190375. FGFR2c ligand binding and activation.
R-HSA-2033514. FGFR3 mutant receptor activation.
R-HSA-2033519. Activated point mutants of FGFR2.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-5654219. Phospholipase C-mediated cascade: FGFR1.
R-HSA-5654221. Phospholipase C-mediated cascade, FGFR2.
R-HSA-5654227. Phospholipase C-mediated cascade, FGFR3.
R-HSA-5654228. Phospholipase C-mediated cascade, FGFR4.
R-HSA-5654687. Downstream signaling of activated FGFR1.
R-HSA-5654688. SHC-mediated cascade:FGFR1.
R-HSA-5654689. PI-3K cascade:FGFR1.
R-HSA-5654693. FRS-mediated FGFR1 signaling.
R-HSA-5654695. PI-3K cascade:FGFR2.
R-HSA-5654699. SHC-mediated cascade:FGFR2.
R-HSA-5654700. FRS-mediated FGFR2 signaling.
R-HSA-5654704. SHC-mediated cascade:FGFR3.
R-HSA-5654706. FRS-mediated FGFR3 signaling.
R-HSA-5654710. PI-3K cascade:FGFR3.
R-HSA-5654712. FRS-mediated FGFR4 signaling.
R-HSA-5654719. SHC-mediated cascade:FGFR4.
R-HSA-5654720. PI-3K cascade:FGFR4.
R-HSA-5654726. Negative regulation of FGFR1 signaling.
R-HSA-5654727. Negative regulation of FGFR2 signaling.
R-HSA-5654732. Negative regulation of FGFR3 signaling.
R-HSA-5654733. Negative regulation of FGFR4 signaling.
R-HSA-5655253. Signaling by FGFR2 in disease.
R-HSA-5655302. Signaling by FGFR1 in disease.
R-HSA-5658623. FGFRL1 modulation of FGFR1 signaling.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-HSA-8853338. Signaling by FGFR3 point mutants in cancer.
SIGNORiQ9GZV9.

Miscellaneous databases

EvolutionaryTraceiQ9GZV9.
GeneWikiiFibroblast_growth_factor_23.
GenomeRNAii8074.
PROiQ9GZV9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000118972.
CleanExiHS_FGF23.
GenevisibleiQ9GZV9. HS.

Family and domain databases

CDDicd00058. FGF. 1 hit.
InterProiIPR008996. Cytokine_IL1-like.
IPR028304. FGF23.
IPR002209. Fibroblast_GF_fam.
IPR028142. IL-1_fam/FGF_fam.
[Graphical view]
PANTHERiPTHR11486. PTHR11486. 1 hit.
PTHR11486:SF69. PTHR11486:SF69. 1 hit.
PfamiPF00167. FGF. 1 hit.
[Graphical view]
PRINTSiPR00262. IL1HBGF.
SMARTiSM00442. FGF. 1 hit.
[Graphical view]
SUPFAMiSSF50353. SSF50353. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiFGF23_HUMAN
AccessioniPrimary (citable) accession number: Q9GZV9
Secondary accession number(s): Q4V758
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: March 1, 2001
Last modified: November 30, 2016
This is version 168 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.