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P31371 (FGF9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 153. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Fibroblast growth factor 9

Short name=FGF-9
Alternative name(s):
Glia-activating factor
Short name=GAF
Heparin-binding growth factor 9
Short name=HBGF-9
Gene names
Name:FGF9
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length208 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. May have a role in glial cell growth and differentiation during development, gliosis during repair and regeneration of brain tissue after damage, differentiation and survival of neuronal cells, and growth stimulation of glial tumors. Ref.8 Ref.9

Subunit structure

Monomer. Homodimer. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Ref.8 Ref.9 Ref.11 Ref.12

Subcellular location

Secreted.

Tissue specificity

Glial cells.

Post-translational modification

Three molecular species were found (30 kDa, 29 kDa and 25 kDa), cleaved at Leu-4, Val-13 and Ser-34 respectively. The smaller ones might be products of proteolytic digestion. Furthermore, there may be a functional signal sequence in the 30 kDa species which is uncleavable in the secretion step.

N-glycosylated.

Involvement in disease

Multiple synostoses syndrome 3 (SYNS3) [MIM:612961]: A bone disease characterized by multiple progressive joint fusions that commonly involve proximal interphalangeal, tarsal-carpal, humeroradial and cervical spine joints. Additional features can include progressive conductive deafness and facial dysmorphism.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13

Miscellaneous

Biochemical analysis of the Asn-99 mutation reveals a significantly impaired FGF signaling, as evidenced by diminished activity of the MAPK1/MAPK2 pathway and decreases CTNNB1 and MYC expression when compared with wild-type protein. Binding of mutant protein to the receptor FGFR3 is severely impaired, although homodimerization of mutant to itself or wild-type is not detectably affected, providing a basis for the observed defective FGF9 signaling.

Sequence similarities

Belongs to the heparin-binding growth factors family.

Ontologies

Keywords
   Biological processDifferentiation
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DiseaseDeafness
Disease mutation
   LigandHeparin-binding
   Molecular functionDevelopmental protein
Growth factor
Mitogen
   PTMGlycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

angiogenesis

Inferred from electronic annotation. Source: Ensembl

cell-cell signaling

Traceable author statement PubMed 8575785. Source: ProtInc

chondrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

embryonic digestive tract development

Inferred from electronic annotation. Source: Ensembl

embryonic limb morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic skeletal system development

Inferred from electronic annotation. Source: Ensembl

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Inferred from genetic interaction Ref.8. Source: MGI

innate immune response

Traceable author statement. Source: Reactome

inner ear morphogenesis

Inferred from electronic annotation. Source: Ensembl

insulin receptor signaling pathway

Traceable author statement. Source: Reactome

lung-associated mesenchyme development

Inferred from electronic annotation. Source: Ensembl

male gonad development

Inferred from expression pattern PubMed 17848411. Source: UniProtKB

male sex determination

Inferred from electronic annotation. Source: Ensembl

negative regulation of Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

positive regulation of MAPK cascade

Inferred from electronic annotation. Source: Ensembl

positive regulation of canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of cardiac muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell division

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of cell proliferation

Inferred from direct assay Ref.1. Source: MGI

positive regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

positive regulation of mesenchymal cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of smoothened signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of vascular endothelial growth factor receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

protein import into nucleus

Inferred from electronic annotation. Source: Ensembl

regulation of timing of cell differentiation

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement PubMed 8575785. Source: ProtInc

substantia nigra development

Inferred from expression pattern PubMed 22926577. Source: UniProt

   Cellular_componentbasement membrane

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from electronic annotation. Source: Ensembl

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay Ref.1. Source: MGI

   Molecular_functiongrowth factor activity

Traceable author statement Ref.1. Source: ProtInc

heparin binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – 33
PRO_0000008973
Chain4 – 208205Fibroblast growth factor 9
PRO_0000008974

Amino acid modifications

Glycosylation791N-linked (GlcNAc...)

Natural variations

Natural variant941I → V. Ref.2
Corresponds to variant rs12427696 [ dbSNP | Ensembl ].
VAR_020944
Natural variant991S → N in SYNS3; expressed and secreted as efficiently as wild-type; however it induces compromised chondrocyte proliferation and differentiation accompanied by enhanced osteogenic differentiation and matrix mineralization of bone marrow-derived mesenchymal stem cells. Ref.13
VAR_063254

Experimental info

Sequence conflict24 – 263VLP → SLL AA sequence Ref.7
Sequence conflict341S → A AA sequence Ref.7

Secondary structure

........................................ 208
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P31371 [UniParc].

Last modified October 1, 1994. Version 3.
Checksum: F32A0E7106EF59C9

FASTA20823,441
        10         20         30         40         50         60 
MAPLGEVGNY FGVQDAVPFG NVPVLPVDSP VLLSDHLGQS EAGGLPRGPA VTDLDHLKGI 

        70         80         90        100        110        120 
LRRRQLYCRT GFHLEIFPNG TIQGTRKDHS RFGILEFISI AVGLVSIRGV DSGLYLGMNE 

       130        140        150        160        170        180 
KGELYGSEKL TQECVFREQF EENWYNTYSS NLYKHVDTGR RYYVALNKDG TPREGTRTKR 

       190        200 
HQKFTHFLPR PVDPDKVPEL YKDILSQS 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of a novel cytokine cDNA encoding the ninth member of the fibroblast growth factor family, which has a unique secretion property."
Miyamoto M., Naruo K., Seko C., Matsumoto S., Kondo T., Kurokawa T.
Mol. Cell. Biol. 13:4251-4259(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Foreskin.
[2]NIEHS SNPs program
Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-94.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.
[4]"The DNA sequence and analysis of human chromosome 13."
Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.
Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]"Novel secretory heparin-binding factors from human glioma cells (glia-activating factors) involved in glial cell growth. Purification and biological properties."
Naruo K., Seko C., Kuroshima K., Matsutani E., Sasada R., Kondo T., Kurokawa T.
J. Biol. Chem. 268:2857-2864(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 4-26 AND 34-54.
Tissue: Glial tumor.
[8]"Receptor specificity of the fibroblast growth factor family."
Ornitz D.M., Xu J., Colvin J.S., McEwen D.G., MacArthur C.A., Coulier F., Gao G., Goldfarb M.
J. Biol. Chem. 271:15292-15297(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FGFR2 AND FGFR3, FUNCTION IN CELL PROLIFERATION.
[9]"Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family."
Zhang X., Ibrahimi O.A., Olsen S.K., Umemori H., Mohammadi M., Ornitz D.M.
J. Biol. Chem. 281:15694-15700(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FGFR1; FGFR2; FGFR3 AND FGFR4, FUNCTION IN STIMULATION OF CELL PROLIFERATION.
[10]"Fibroblast growth factor signalling: from development to cancer."
Turner N., Grose R.
Nat. Rev. Cancer 10:116-129(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[11]"Structure of fibroblast growth factor 9 shows a symmetric dimer with unique receptor- and heparin-binding interfaces."
Hecht H.J., Adar R., Hofmann B., Bogin O., Weich H., Yayon A.
Acta Crystallogr. D 57:378-384(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS), SUBUNIT, HEPARIN-BINDING.
[12]"Crystal structure of fibroblast growth factor 9 reveals regions implicated in dimerization and autoinhibition."
Plotnikov A.N., Eliseenkova A.V., Ibrahimi O.A., Shriver Z., Sasisekharan R., Lemmon M.A., Mohammadi M.
J. Biol. Chem. 276:4322-4329(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 35-208, SUBUNIT.
[13]"Multiple synostoses syndrome is due to a missense mutation in exon 2 of FGF9 gene."
Wu X.L., Gu M.M., Huang L., Liu X.S., Zhang H.X., Ding X.Y., Xu J.Q., Cui B., Wang L., Lu S.Y., Chen X.Y., Zhang H.G., Huang W., Yuan W.T., Yang J.M., Gu Q., Fei J., Chen Z., Yuan Z.M., Wang Z.G.
Am. J. Hum. Genet. 85:53-63(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SYNS3 ASN-99, CHARACTERIZATION OF VARIANT SYNS3 ASN-99.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D14838 mRNA. Translation: BAA03572.1.
AY682094 Genomic DNA. Translation: AAT74624.1.
AK290792 mRNA. Translation: BAF83481.1.
AL139378 Genomic DNA. Translation: CAC17692.1.
CH471075 Genomic DNA. Translation: EAX08316.1.
BC069692 mRNA. Translation: AAH69692.1.
BC103978 mRNA. Translation: AAI03979.1.
BC103979 mRNA. Translation: AAI03980.1.
CCDSCCDS9298.1.
PIRA48137.
RefSeqNP_002001.1. NM_002010.2.
UniGeneHs.111.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1G82X-ray2.60A/B/C/D49-208[»]
1IHKX-ray2.20A35-208[»]
ProteinModelPortalP31371.
SMRP31371. Positions 52-208.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108545. 2 interactions.
DIPDIP-6036N.
STRING9606.ENSP00000371790.

PTM databases

PhosphoSiteP31371.

Polymorphism databases

DMDM544290.

Proteomic databases

PaxDbP31371.
PRIDEP31371.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000382353; ENSP00000371790; ENSG00000102678.
GeneID2254.
KEGGhsa:2254.
UCSCuc001uog.2. human.

Organism-specific databases

CTD2254.
GeneCardsGC13P022245.
HGNCHGNC:3687. FGF9.
HPACAB004392.
MIM600921. gene.
612961. phenotype.
neXtProtNX_P31371.
Orphanet3237. Multiple synostoses syndrome.
PharmGKBPA28126.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG269410.
HOGENOMHOG000236341.
HOVERGENHBG007580.
InParanoidP31371.
KOK04358.
OMAGELYGSD.
OrthoDBEOG7992S1.
PhylomeDBP31371.
TreeFamTF317805.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.
SignaLinkP31371.

Gene expression databases

BgeeP31371.
CleanExHS_FGF9.
GenevestigatorP31371.

Family and domain databases

InterProIPR008996. Cytokine_IL1-like.
IPR028251. FGF9.
IPR002209. Fibroblast_GF_fam.
IPR028142. IL-1_fam/FGF_fam.
[Graphical view]
PANTHERPTHR11486. PTHR11486. 1 hit.
PTHR11486:SF28. PTHR11486:SF28. 1 hit.
PfamPF00167. FGF. 1 hit.
[Graphical view]
PRINTSPR00263. HBGFFGF.
PR00262. IL1HBGF.
SMARTSM00442. FGF. 1 hit.
[Graphical view]
SUPFAMSSF50353. SSF50353. 1 hit.
PROSITEPS00247. HBGF_FGF. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP31371.
GeneWikiFGF9.
GenomeRNAi2254.
NextBio9131.
PROP31371.
SOURCESearch...

Entry information

Entry nameFGF9_HUMAN
AccessionPrimary (citable) accession number: P31371
Secondary accession number(s): A8K427, Q3SY32
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: October 1, 1994
Last modified: July 9, 2014
This is version 153 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 13

Human chromosome 13: entries, gene names and cross-references to MIM