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Protein

Fibroblast growth factor 4

Gene

FGF4

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

Functioni

Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation. Required for normal limb and cardiac valve development during embryogenesis.1 Publication

GO - Molecular functioni

  • growth factor activity Source: ProtInc
  • heparin binding Source: UniProtKB-KW

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Growth factor, Mitogen

Keywords - Biological processi

Differentiation

Keywords - Ligandi

Heparin-binding

Enzyme and pathway databases

ReactomeiREACT_110235. Phospholipase C-mediated cascade: FGFR1.
REACT_120863. Activated point mutants of FGFR2.
REACT_121153. Signaling by activated point mutants of FGFR1.
REACT_121249. FGFR3 mutant receptor activation.
REACT_121337. Signaling by activated point mutants of FGFR3.
REACT_147727. Constitutive Signaling by Aberrant PI3K in Cancer.
REACT_355069. FRS-mediated FGFR2 signaling.
REACT_355144. Negative regulation of FGFR3 signaling.
REACT_355146. Phospholipase C-mediated cascade, FGFR2.
REACT_355159. SHC-mediated cascade:FGFR4.
REACT_355160. PI-3K cascade:FGFR3.
REACT_355194. SHC-mediated cascade:FGFR1.
REACT_355197. SHC-mediated cascade:FGFR3.
REACT_355202. Signaling by FGFR4 mutants.
REACT_355212. FRS-mediated FGFR3 signaling.
REACT_355216. Phospholipase C-mediated cascade, FGFR4.
REACT_355218. Negative regulation of FGFR1 signaling.
REACT_355221. Signaling by FGFR1 mutants.
REACT_355225. SHC-mediated cascade:FGFR2.
REACT_355227. Negative regulation of FGFR2 signaling.
REACT_355304. PI-3K cascade:FGFR4.
REACT_355313. Signaling by FGFR3 mutants.
REACT_355450. PI-3K cascade:FGFR2.
REACT_355511. Signaling by FGFR2 mutants.
REACT_355514. Phospholipase C-mediated cascade, FGFR3.
REACT_355552. PI-3K cascade:FGFR1.
REACT_355580. FRS2-mediated FGFR4 signaling.
REACT_355584. FRS-mediated FGFR1 signaling.
REACT_355588. Negative regulation of FGFR4 signaling.
REACT_75829. PIP3 activates AKT signaling.
REACT_9413. FGFR2c ligand binding and activation.
REACT_9452. FGFR4 ligand binding and activation.
REACT_9510. FGFR3c ligand binding and activation.
REACT_9515. FGFR1c ligand binding and activation.
REACT_976. PI3K Cascade.
SignaLinkiP08620.

Names & Taxonomyi

Protein namesi
Recommended name:
Fibroblast growth factor 4
Short name:
FGF-4
Alternative name(s):
Heparin secretory-transforming protein 1
Short name:
HST
Short name:
HST-1
Short name:
HSTF-1
Heparin-binding growth factor 4
Short name:
HBGF-4
Transforming protein KS3
Gene namesi
Name:FGF4
Synonyms:HST, HSTF1, KS3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:3682. FGF4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

PharmGKBiPA28121.

Chemistry

DrugBankiDB00686. Pentosan Polysulfate.

Polymorphism and mutation databases

BioMutaiFGF4.
DMDMi122750.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3030Sequence AnalysisAdd
BLAST
Chaini31 – 206176Fibroblast growth factor 4PRO_0000008953Add
BLAST

Proteomic databases

PaxDbiP08620.
PRIDEiP08620.

PTM databases

PhosphoSiteiP08620.

Expressioni

Gene expression databases

BgeeiP08620.
CleanExiHS_FGF4.
GenevestigatoriP08620.

Organism-specific databases

HPAiHPA011209.

Interactioni

Subunit structurei

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.1 Publication

Protein-protein interaction databases

DIPiDIP-4017N.
STRINGi9606.ENSP00000168712.

Structurei

Secondary structure

1
206
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi82 – 887Combined sources
Beta strandi94 – 985Combined sources
Beta strandi104 – 1096Combined sources
Helixi112 – 1143Combined sources
Beta strandi116 – 1227Combined sources
Beta strandi125 – 1306Combined sources
Turni131 – 1344Combined sources
Beta strandi135 – 1395Combined sources
Beta strandi145 – 1506Combined sources
Beta strandi155 – 1617Combined sources
Helixi163 – 1653Combined sources
Beta strandi167 – 1748Combined sources
Beta strandi185 – 1873Combined sources
Helixi190 – 1923Combined sources
Helixi198 – 2003Combined sources
Beta strandi202 – 2054Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IJTX-ray1.80A79-206[»]
ProteinModelPortaliP08620.
SMRiP08620. Positions 79-206.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08620.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG290420.
GeneTreeiENSGT00760000118859.
HOGENOMiHOG000236341.
HOVERGENiHBG007580.
InParanoidiP08620.
KOiK04358.
OMAiYNAYESH.
OrthoDBiEOG7992S1.
PhylomeDBiP08620.
TreeFamiTF317805.

Family and domain databases

InterProiIPR008996. Cytokine_IL1-like.
IPR028239. FGF4.
IPR002209. Fibroblast_GF_fam.
IPR028142. IL-1_fam/FGF_fam.
[Graphical view]
PANTHERiPTHR11486. PTHR11486. 1 hit.
PTHR11486:SF31. PTHR11486:SF31. 1 hit.
PRINTSiPR00263. HBGFFGF.
PR00262. IL1HBGF.
SMARTiSM00442. FGF. 1 hit.
[Graphical view]
SUPFAMiSSF50353. SSF50353. 1 hit.
PROSITEiPS00247. HBGF_FGF. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P08620-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSGPGTAAVA LLPAVLLALL APWAGRGGAA APTAPNGTLE AELERRWESL
60 70 80 90 100
VALSLARLPV AAQPKEAAVQ SGAGDYLLGI KRLRRLYCNV GIGFHLQALP
110 120 130 140 150
DGRIGGAHAD TRDSLLELSP VERGVVSIFG VASRFFVAMS SKGKLYGSPF
160 170 180 190 200
FTDECTFKEI LLPNNYNAYE SYKYPGMFIA LSKNGKTKKG NRVSPTMKVT

HFLPRL
Length:206
Mass (Da):22,048
Last modified:August 1, 1988 - v1
Checksum:iC7FD54A0272A1569
GO
Isoform 2 (identifier: P08620-2) [UniParc]FASTAAdd to basket

Also known as: FGF4si

The sequence of this isoform differs from the canonical sequence as follows:
     114-206: SLLELSPVER...MKVTHFLPRL → TLLHR

Note: Antagonist of isoform 1, shutting down FGF4-induced Erk1/2 phosphorylation.

Show »
Length:118
Mass (Da):12,237
Checksum:iAAA97FBB8C667D7F
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei114 – 20693SLLEL…FLPRL → TLLHR in isoform 2. 1 PublicationVSP_053541Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FJ456981 mRNA. Translation: ACJ68447.1.
J02986 Genomic DNA. Translation: AAB59555.1.
M17446 mRNA. Translation: AAA59473.1.
CCDSiCCDS8194.1. [P08620-1]
PIRiA28417. TVHUHS.
RefSeqiNP_001998.1. NM_002007.2. [P08620-1]
XP_005273904.1. XM_005273847.1. [P08620-2]
XP_006718538.1. XM_006718475.2. [P08620-1]
UniGeneiHs.1755.

Genome annotation databases

EnsembliENST00000168712; ENSP00000168712; ENSG00000075388. [P08620-1]
GeneIDi2249.
KEGGihsa:2249.
UCSCiuc001opg.1. human. [P08620-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FJ456981 mRNA. Translation: ACJ68447.1.
J02986 Genomic DNA. Translation: AAB59555.1.
M17446 mRNA. Translation: AAA59473.1.
CCDSiCCDS8194.1. [P08620-1]
PIRiA28417. TVHUHS.
RefSeqiNP_001998.1. NM_002007.2. [P08620-1]
XP_005273904.1. XM_005273847.1. [P08620-2]
XP_006718538.1. XM_006718475.2. [P08620-1]
UniGeneiHs.1755.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IJTX-ray1.80A79-206[»]
ProteinModelPortaliP08620.
SMRiP08620. Positions 79-206.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-4017N.
STRINGi9606.ENSP00000168712.

Chemistry

ChEMBLiCHEMBL3286072.
DrugBankiDB00686. Pentosan Polysulfate.

PTM databases

PhosphoSiteiP08620.

Polymorphism and mutation databases

BioMutaiFGF4.
DMDMi122750.

Proteomic databases

PaxDbiP08620.
PRIDEiP08620.

Protocols and materials databases

DNASUi2249.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000168712; ENSP00000168712; ENSG00000075388. [P08620-1]
GeneIDi2249.
KEGGihsa:2249.
UCSCiuc001opg.1. human. [P08620-1]

Organism-specific databases

CTDi2249.
GeneCardsiGC11M069588.
HGNCiHGNC:3682. FGF4.
HPAiHPA011209.
MIMi164980. gene.
neXtProtiNX_P08620.
PharmGKBiPA28121.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG290420.
GeneTreeiENSGT00760000118859.
HOGENOMiHOG000236341.
HOVERGENiHBG007580.
InParanoidiP08620.
KOiK04358.
OMAiYNAYESH.
OrthoDBiEOG7992S1.
PhylomeDBiP08620.
TreeFamiTF317805.

Enzyme and pathway databases

ReactomeiREACT_110235. Phospholipase C-mediated cascade: FGFR1.
REACT_120863. Activated point mutants of FGFR2.
REACT_121153. Signaling by activated point mutants of FGFR1.
REACT_121249. FGFR3 mutant receptor activation.
REACT_121337. Signaling by activated point mutants of FGFR3.
REACT_147727. Constitutive Signaling by Aberrant PI3K in Cancer.
REACT_355069. FRS-mediated FGFR2 signaling.
REACT_355144. Negative regulation of FGFR3 signaling.
REACT_355146. Phospholipase C-mediated cascade, FGFR2.
REACT_355159. SHC-mediated cascade:FGFR4.
REACT_355160. PI-3K cascade:FGFR3.
REACT_355194. SHC-mediated cascade:FGFR1.
REACT_355197. SHC-mediated cascade:FGFR3.
REACT_355202. Signaling by FGFR4 mutants.
REACT_355212. FRS-mediated FGFR3 signaling.
REACT_355216. Phospholipase C-mediated cascade, FGFR4.
REACT_355218. Negative regulation of FGFR1 signaling.
REACT_355221. Signaling by FGFR1 mutants.
REACT_355225. SHC-mediated cascade:FGFR2.
REACT_355227. Negative regulation of FGFR2 signaling.
REACT_355304. PI-3K cascade:FGFR4.
REACT_355313. Signaling by FGFR3 mutants.
REACT_355450. PI-3K cascade:FGFR2.
REACT_355511. Signaling by FGFR2 mutants.
REACT_355514. Phospholipase C-mediated cascade, FGFR3.
REACT_355552. PI-3K cascade:FGFR1.
REACT_355580. FRS2-mediated FGFR4 signaling.
REACT_355584. FRS-mediated FGFR1 signaling.
REACT_355588. Negative regulation of FGFR4 signaling.
REACT_75829. PIP3 activates AKT signaling.
REACT_9413. FGFR2c ligand binding and activation.
REACT_9452. FGFR4 ligand binding and activation.
REACT_9510. FGFR3c ligand binding and activation.
REACT_9515. FGFR1c ligand binding and activation.
REACT_976. PI3K Cascade.
SignaLinkiP08620.

Miscellaneous databases

EvolutionaryTraceiP08620.
GeneWikiiFGF4.
GenomeRNAii2249.
NextBioi35478625.
PROiP08620.
SOURCEiSearch...

Gene expression databases

BgeeiP08620.
CleanExiHS_FGF4.
GenevestigatoriP08620.

Family and domain databases

InterProiIPR008996. Cytokine_IL1-like.
IPR028239. FGF4.
IPR002209. Fibroblast_GF_fam.
IPR028142. IL-1_fam/FGF_fam.
[Graphical view]
PANTHERiPTHR11486. PTHR11486. 1 hit.
PTHR11486:SF31. PTHR11486:SF31. 1 hit.
PRINTSiPR00263. HBGFFGF.
PR00262. IL1HBGF.
SMARTiSM00442. FGF. 1 hit.
[Graphical view]
SUPFAMiSSF50353. SSF50353. 1 hit.
PROSITEiPS00247. HBGF_FGF. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Fibroblast growth factor 4 and its novel splice isoform have opposing effects on the maintenance of human embryonic stem cell self-renewal."
    Mayshar Y., Rom E., Chumakov I., Kronman A., Yayon A., Benvenisty N.
    Stem Cells 26:767-774(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING.
  2. "Genomic sequence of hst, a transforming gene encoding a protein homologous to fibroblast growth factors and the int-2-encoded protein."
    Yoshida T., Miyagawa K., Odagiri H., Sakamoto H., Little P.F.R., Terada M., Sugimura T.
    Proc. Natl. Acad. Sci. U.S.A. 84:7305-7309(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "cDNA sequence of human transforming gene hst and identification of the coding sequence required for transforming activity."
    Taira M., Yoshida T., Miyagawa K., Sakamoto H., Terada M., Sugimura T.
    Proc. Natl. Acad. Sci. U.S.A. 84:2980-2984(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "An oncogene isolated by transfection of Kaposi's sarcoma DNA encodes a growth factor that is a member of the FGF family."
    Delli-Bovi P., Curatola A.M., Kern F.G., Greco A., Ittmann M., Basilico C.
    Cell 50:729-737(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  5. Cited for: INTERACTION WITH FGFR1; FGFR2; FGFR3 AND FGFR4, FUNCTION IN CELL PROLIFERATION.
  6. "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.
  7. "Identification of receptor and heparin binding sites in fibroblast growth factor 4 by structure-based mutagenesis."
    Bellosta P., Iwahori A., Plotnikov A.N., Eliseenkova A.V., Basilico C., Mohammadi M.
    Mol. Cell. Biol. 21:5946-5957(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 79-206.

Entry informationi

Entry nameiFGF4_HUMAN
AccessioniPrimary (citable) accession number: P08620
Secondary accession number(s): B7U994
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: May 27, 2015
This is version 150 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, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.