Fibroblast growth factor 23 precursor

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Reviewed, UniProtKB/Swiss-Prot Q9GZV9 (FGF23_HUMAN)

Last modified June 16, 2009. Version 95. History...

Clusters with 100%, 90%, 50% identity |

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Fibroblast growth factor 23
      Short name=FGF-23
Alternative name(s):
    Tumor-derived hypophosphatemia-inducing factor
    Phosphatonin
Cleaved into the following 2 chains:
    1- Recommended name:
            Fibroblast growth factor 23 N-terminal peptide
    2- Recommended name:
            Fibroblast growth factor 23 C-terminal peptide

Gene names

Name:	FGF23
Synonyms:	HYPF
ORF Names:	UNQ3027/PRO9828

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	251 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Subcellular location	Secreted.
Post-translational modification	After secretion it is processed into a N-terminal fragment and a C-terminal fragment. The processing is effected by the proprotein convertases.
Involvement in disease	Defects in FGF23 are the cause of autosomal dominant hypophosphataemic rickets (ADHR) [MIM:193100]. ADHR is characterized by low serum phosphorus concentrations, rickets, osteomalacia, leg deformities, short stature, bone pain and dental abscesses. Ref.2 Defects in FGF23 are a cause of hyperphosphatemic familial tumoral calcinosis (HFTC) [MIM:211900]. HFTC is a severe autosomal recessive metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues. Ref.12
Sequence similarities	Belongs to the heparin-binding growth factors family.

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Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Molecular function	Growth factor
PTM	Disulfide bond
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cell differentiation Non-traceable author statement. Source: UniProtKB fibroblast growth factor receptor signaling pathway Inferred from Experiment. Source: Reactome
Cellular component	extracellular space Non-traceable author statement. Source: UniProtKB
Molecular function	growth factor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

Ref.7

Chain

25 – 251

227

Fibroblast growth factor 23

PRO_0000008998

Chain

25 – 179

155

Fibroblast growth factor 23 N-terminal peptide

PRO_0000352875

Chain

180 – 251

Fibroblast growth factor 23 C-terminal peptide

PRO_0000352876

Sites

Site

179 – 180

Cleavage; by proprotein convertases

Amino acid modifications

Disulfide bond

95 ↔ 113

Natural variations

Natural variant

S → G in HFTC; only the C-terminal fragment is secreted, whereas the intact protein is retained in the Golgi complex. Ref.12

VAR_023831

Natural variant

176

R → Q in ADHR. Ref.2

VAR_010717

Natural variant

179

R → Q in ADHR; C-terminal processing is abolished. Ref.2

VAR_010719

Natural variant

179

R → W in ADHR; C-terminal processing is abolished. Ref.2

VAR_010718

Natural variant

195

P → S: dbSNP rs13312793. Ref.5

VAR_018887

Natural variant

239

T → M: dbSNP rs7955866. Ref.2 Ref.5

VAR_010720

Secondary structure

251

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

Q9GZV9-1 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 6093BD0CC50C2489
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FASTA

251

27,954

        10         20         30         40         50         60 
MLGARLRLWV CALCSVCSMS VLRAYPNASP LLGSSWGGLI HLYTATARNS YHLQIHKNGH 

        70         80         90        100        110        120 
VDGAPHQTIY SALMIRSEDA GFVVITGVMS RRYLCMDFRG NIFGSHYFDP ENCRFQHQTL 

       130        140        150        160        170        180 
ENGYDVYHSP QYHFLVSLGR AKRAFLPGMN PPPYSQFLSR RNEIPLIHFN TPIPRRHTRS 

       190        200        210        220        230        240 
AEDDSERDPL NVLKPRARMT PAPASCSQEL PSAEDNSPMA SDPLGVVRGG RVNTHAGGTG 

       250 
PEGCRPFAKF I

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain." Yamashita T., Yoshioka M., Itoh N. Biochem. Biophys. Res. Commun. 277:494-498(2000) [PubMed: 11032749] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23." White K.E., Evans W.E., O'Riordan J.L.H., Speer M.C., Econs M.J., Lorenz-Depiereux B., Grabowski M., Meitinger T., Strom T.M. Nat. Genet. 26:345-348(2000) [PubMed: 11062477] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ADHR GLN-176; GLN-179 AND TRP-179, VARIANT MET-239.
[3]	"Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia." Shimada T., Mizutani S., Muto T., Yoneya T., Hino R., Takeda S., Takeuchi Y., Fujita T., Fukumoto S., Yamashita T. Proc. Natl. Acad. Sci. U.S.A. 98:6500-6505(2001) [PubMed: 11344269] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	NIEHS SNPs program Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-195 AND MET-239.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-39.
[8]	"The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting." White K.E., Jonsson K.B., Carn G., Hampson G., Spector T.D., Mannstadt M., Lorenz-Depiereux B., Miyauchi A., Yang I.M., Ljunggren O., Meitinger T., Strom T.M., Jueppner H., Econs M.J. J. Clin. Endocrinol. Metab. 86:497-500(2001) [PubMed: 11157998] [Abstract] Cited for: PROCESSING.
[9]	"Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes hypophosphatemia in vivo." Shimada T., Muto T., Urakawa I., Yoneya T., Yamazaki Y., Okawa K., Takeuchi Y., Fujita T., Fukumoto S., Yamashita T. Endocrinology 143:3179-3182(2002) [PubMed: 12130585] [Abstract] Cited for: PROCESSING.
[10]	"FGF23 is processed by proprotein convertases but not by PHEX." Benet-Pages A., Lorenz-Depiereux B., Zischka H., White K.E., Econs M.J., Strom T.M. Bone 35:455-462(2004) [PubMed: 15268897] [Abstract] Cited for: PROCESSING BY PROPROTEIN CONVERTASES.
[11]	"Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members." Goetz R., Beenken A., Ibrahimi O.A., Kalinina J., Olsen S.K., Eliseenkova A.V., Xu C., Neubert T.A., Zhang F., Linhardt R.J., Yu X., White K.E., Inagaki T., Kliewer S.A., Yamamoto M., Kurosu H., Ogawa Y., Kuro-o M. , Lanske B., Razzaque M.S., Mohammadi M. Mol. Cell. Biol. 27:3417-3428(2007) [PubMed: 17339340] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 25-179.
[12]	"An FGF23 missense mutation causes familial tumoral calcinosis with hyperphosphatemia." Benet-Pages A., Orlik P., Strom T.M., Lorenz-Depiereux B. Hum. Mol. Genet. 14:385-390(2005) [PubMed: 15590700] [Abstract] Cited for: VARIANT HFTC GLY-71.
+	Additional computationally mapped references.

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Web resources

GeneReviews

NIEHS-SNPs

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Cross-references

Sequence databases

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.

IPI

IPI00026407.

RefSeq

NP_065689.1.

UniGene

Hs.287370

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2P39	X-ray	1.50	A	25-179	[»]

ModBase

Search...

Proteomic databases

PRIDE

Q9GZV9.

Genome annotation databases

Ensembl

ENSG00000118972. Homo sapiens. [Contig view]

GeneID

8074.

KEGG

hsa:8074.

NMPDR

fig|9606.3.peg.6984.

Organism-specific databases

GeneCards

GC12M004347.

H-InvDB

HIX0036668.

HGNC

HGNC:3680. FGF23.

MIM

193100. phenotype.
211900. phenotype.
605380. gene.

Orphanet

53715. Calcinosis, tumoral.
437. Vitamin D resistant rickets.

PharmGKB

PA28119.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q9GZV9.

HOVERGEN

Q9GZV9.

OMA

Q9GZV9. ASDPLGV.

Enzyme and pathway databases

Pathway_Interaction_DB

fgf_pathway. FGF signaling pathway.

Reactome

REACT_9470. Signaling by FGFR.

Gene expression databases

ArrayExpress

Q9GZV9.

Bgee

Q9GZV9.

CleanEx

HS_FGF23.

GermOnline

ENSG00000118972. Homo sapiens.

Family and domain databases

InterPro

IPR002348. IL1_HBGF.
[Graphical view]

PANTHER

PTHR11486. IL1_HBGF. 1 hit.

Pfam

PF00167. FGF. 1 hit.
[Graphical view]

PRINTS

PR00262. IL1HBGF.

ProDom

PD000831. IL1_HBGF. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00442. FGF. 1 hit.
[Graphical view]

PROSITE

PS00247. HBGF_FGF. False negative.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

30678.

SOURCE

Search...

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Entry information

Entry name

FGF23_HUMAN

Accession

Primary (citable) accession number: Q9GZV9
Secondary accession number(s): Q4V758

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	March 1, 2001
Last modified:	June 16, 2009
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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