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Protein

Fibroblast growth factor 23

Gene

FGF23

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionGrowth factor
Biological processDifferentiation

Enzyme and pathway databases

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-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
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
R-HSA-8957275 Post-translational protein phosphorylation

Protein family/group databases

TCDBi1.A.108.1.2 the fibroblast growth factor 2 (fgf2) family

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

EuPathDBiHostDB:ENSG00000118972.1
HGNCiHGNC:3680 FGF23
MIMi605380 gene
neXtProtiNX_Q9GZV9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Hypophosphatemic rickets, autosomal dominant (ADHR)3 Publications
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 dbSNP:rs104894347EnsemblClinVar.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 dbSNP:rs193922702EnsemblClinVar.1
Natural variantiVAR_010718179R → W in ADHR; C-terminal processing is abolished. 1 PublicationCorresponds to variant dbSNP:rs28937882EnsemblClinVar.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 dbSNP:rs104894342EnsemblClinVar.1
Natural variantiVAR_07171196M → T in HFTC. 1 PublicationCorresponds to variant dbSNP:rs104894343EnsemblClinVar.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 dbSNP:rs104894344EnsemblClinVar.1
Natural variantiVAR_071713157F → L in HFTC. 1 PublicationCorresponds to variant dbSNP:rs772964687Ensembl.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

Chemistry databases

ChEMBLiCHEMBL3713913

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) threonine1 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

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113748, 2 interactors
CORUMiQ9GZV9
DIPiDIP-58507N
IntActiQ9GZV9, 6 interactors
STRINGi9606.ENSP00000237837

Structurei

Secondary structure

1251
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi32 – 36Combined sources5
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 strandi121 – 123Combined sources3
Beta strandi125 – 128Combined sources4
Turni130 – 132Combined sources3
Beta strandi138 – 140Combined sources3
Beta strandi147 – 149Combined 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[»]
5W21X-ray3.00B25-204[»]
ProteinModelPortaliQ9GZV9
SMRiQ9GZV9
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9GZV9

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3885 Eukaryota
ENOG4111IPH LUCA
GeneTreeiENSGT00530000063469
HOGENOMiHOG000112573
HOVERGENiHBG051613
InParanoidiQ9GZV9
KOiK22428
OMAiQIHKDGH
OrthoDBiEOG091G0NAY
PhylomeDBiQ9GZV9
TreeFamiTF335872

Family and domain databases

CDDicd00058 FGF, 1 hit
InterProiView protein in InterPro
IPR028304 FGF23
IPR002209 Fibroblast_GF_fam
IPR008996 IL1/FGF
PANTHERiPTHR11486 PTHR11486, 1 hit
PTHR11486:SF69 PTHR11486:SF69, 1 hit
PfamiView protein in Pfam
PF00167 FGF, 1 hit
SMARTiView protein in SMART
SM00442 FGF, 1 hit
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 dbSNP:rs104894342EnsemblClinVar.1
Natural variantiVAR_07171196M → T in HFTC. 1 PublicationCorresponds to variant dbSNP:rs104894343EnsemblClinVar.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 dbSNP:rs104894344EnsemblClinVar.1
Natural variantiVAR_071713157F → L in HFTC. 1 PublicationCorresponds to variant dbSNP:rs772964687Ensembl.1
Natural variantiVAR_010717176R → Q in ADHR; partially resistant to cleavage by furin. 2 PublicationsCorresponds to variant dbSNP:rs104894347EnsemblClinVar.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 dbSNP:rs193922702EnsemblClinVar.1
Natural variantiVAR_010718179R → W in ADHR; C-terminal processing is abolished. 1 PublicationCorresponds to variant dbSNP:rs28937882EnsemblClinVar.1
Natural variantiVAR_018887195P → S1 PublicationCorresponds to variant dbSNP:rs13312793Ensembl.1
Natural variantiVAR_010720239T → M2 PublicationsCorresponds to variant dbSNP:rs7955866EnsemblClinVar.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

Similar proteinsi

Entry informationi

Entry nameiFGF23_HUMAN
AccessioniPrimary (citable) accession number: Q9GZV9
Secondary accession number(s): Q4V758
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: March 1, 2001
Last modified: April 25, 2018
This is version 181 of the entry and version 1 of the sequence. See 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

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