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P08620

- FGF4_HUMAN

UniProt

P08620 - FGF4_HUMAN

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Protein

Fibroblast growth factor 4

Gene

FGF4

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. growth factor activity Source: ProtInc
  2. heparin binding Source: UniProtKB-KW

GO - Biological processi

  1. apoptotic process involved in morphogenesis Source: Ensembl
  2. cartilage condensation Source: Ensembl
  3. cell-cell signaling Source: ProtInc
  4. chondroblast differentiation Source: UniProtKB
  5. cranial suture morphogenesis Source: Ensembl
  6. embryonic hindlimb morphogenesis Source: Ensembl
  7. epidermal growth factor receptor signaling pathway Source: Reactome
  8. Fc-epsilon receptor signaling pathway Source: Reactome
  9. fibroblast growth factor receptor signaling pathway Source: MGI
  10. innate immune response Source: Reactome
  11. insulin receptor signaling pathway Source: Reactome
  12. mesenchymal cell proliferation Source: UniProtKB
  13. negative regulation of apoptotic process Source: Ensembl
  14. neurotrophin TRK receptor signaling pathway Source: Reactome
  15. odontogenesis of dentin-containing tooth Source: Ensembl
  16. phosphatidylinositol-mediated signaling Source: Reactome
  17. positive regulation of cell division Source: UniProtKB-KW
  18. positive regulation of cell proliferation Source: MGI
  19. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  20. positive regulation of protein phosphorylation Source: Ensembl
  21. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  22. signal transduction Source: ProtInc
  23. stem cell maintenance Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Growth factor, Mitogen

Keywords - Biological processi

Differentiation

Keywords - Ligandi

Heparin-binding

Enzyme and pathway databases

ReactomeiREACT_111184. Negative regulation of FGFR signaling.
REACT_120863. Activated point mutants of FGFR2.
REACT_121153. Signaling by activated point mutants of FGFR1.
REACT_121249. Signaling by FGFR3 mutants.
REACT_121337. Signaling by activated point mutants of FGFR3.
REACT_121398. Signaling by FGFR mutants.
REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
REACT_21247. FRS2-mediated cascade.
REACT_21270. PI-3K cascade.
REACT_21310. Phospholipase C-mediated cascade.
REACT_21374. SHC-mediated cascade.
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: Chromosome 11

Organism-specific databases

HGNCiHGNC:3682. FGF4.

Subcellular locationi

Secreted Curated

GO - Cellular componenti

  1. cytosol Source: Ensembl
  2. extracellular region Source: Reactome
  3. nucleus Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

PharmGKBiPA28121.

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 – 887
Beta strandi94 – 985
Beta strandi104 – 1096
Helixi112 – 1143
Beta strandi116 – 1227
Beta strandi125 – 1306
Turni131 – 1344
Beta strandi135 – 1395
Beta strandi145 – 1506
Beta strandi155 – 1617
Helixi163 – 1653
Beta strandi167 – 1748
Beta strandi185 – 1873
Helixi190 – 1923
Helixi198 – 2003
Beta strandi202 – 2054

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
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. Align

Isoform 1 (identifier: P08620) [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:
EMBL
GenBank
DDBJ
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_006718475.1. [P08620-1]
UniGeneiHs.1755.

Genome annotation databases

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

Polymorphism databases

DMDMi122750.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
FJ456981 mRNA. Translation: ACJ68447.1 .
J02986 Genomic DNA. Translation: AAB59555.1 .
M17446 mRNA. Translation: AAA59473.1 .
CCDSi CCDS8194.1. [P08620-1 ]
PIRi A28417. TVHUHS.
RefSeqi NP_001998.1. NM_002007.2. [P08620-1 ]
XP_005273904.1. XM_005273847.1. [P08620-2 ]
XP_006718538.1. XM_006718475.1. [P08620-1 ]
UniGenei Hs.1755.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1IJT X-ray 1.80 A 79-206 [» ]
ProteinModelPortali P08620.
SMRi P08620. Positions 79-206.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-4017N.
STRINGi 9606.ENSP00000168712.

Chemistry

DrugBanki DB00686. Pentosan Polysulfate.

PTM databases

PhosphoSitei P08620.

Polymorphism databases

DMDMi 122750.

Proteomic databases

PaxDbi P08620.
PRIDEi P08620.

Protocols and materials databases

DNASUi 2249.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000168712 ; ENSP00000168712 ; ENSG00000075388 . [P08620-1 ]
GeneIDi 2249.
KEGGi hsa:2249.
UCSCi uc001opg.1. human. [P08620-1 ]

Organism-specific databases

CTDi 2249.
GeneCardsi GC11M069588.
HGNCi HGNC:3682. FGF4.
HPAi HPA011209.
MIMi 164980. gene.
neXtProti NX_P08620.
PharmGKBi PA28121.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG290420.
GeneTreei ENSGT00760000118859.
HOGENOMi HOG000236341.
HOVERGENi HBG007580.
InParanoidi P08620.
KOi K04358.
OMAi YNAYESH.
OrthoDBi EOG7992S1.
PhylomeDBi P08620.
TreeFami TF317805.

Enzyme and pathway databases

Reactomei REACT_111184. Negative regulation of FGFR signaling.
REACT_120863. Activated point mutants of FGFR2.
REACT_121153. Signaling by activated point mutants of FGFR1.
REACT_121249. Signaling by FGFR3 mutants.
REACT_121337. Signaling by activated point mutants of FGFR3.
REACT_121398. Signaling by FGFR mutants.
REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
REACT_21247. FRS2-mediated cascade.
REACT_21270. PI-3K cascade.
REACT_21310. Phospholipase C-mediated cascade.
REACT_21374. SHC-mediated cascade.
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.
SignaLinki P08620.

Miscellaneous databases

EvolutionaryTracei P08620.
GeneWikii FGF4.
GenomeRNAii 2249.
NextBioi 35478625.
PROi P08620.
SOURCEi Search...

Gene expression databases

Bgeei P08620.
CleanExi HS_FGF4.
Genevestigatori P08620.

Family and domain databases

InterProi IPR008996. Cytokine_IL1-like.
IPR028239. FGF4.
IPR002209. Fibroblast_GF_fam.
IPR028142. IL-1_fam/FGF_fam.
[Graphical view ]
PANTHERi PTHR11486. PTHR11486. 1 hit.
PTHR11486:SF31. PTHR11486:SF31. 1 hit.
PRINTSi PR00263. HBGFFGF.
PR00262. IL1HBGF.
SMARTi SM00442. FGF. 1 hit.
[Graphical view ]
SUPFAMi SSF50353. SSF50353. 1 hit.
PROSITEi PS00247. HBGF_FGF. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: October 29, 2014
This is version 144 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