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Protein

Fibroblast growth factor 1

Gene

FGF1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro. Acts as a ligand for FGFR1 and integrins. Binds to FGFR1 in the presence of heparin leading to FGFR1 dimerization and activation via sequential autophosphorylation on tyrosine residues which act as docking sites for interacting proteins, leading to the activation of several signaling cascades. Binds to integrin ITGAV:ITGB3. Its binding to integrin, subsequent ternary complex formation with integrin and FGFR1, and the recruitment of PTPN11 to the complex are essential for FGF1 signaling. Induces the phosphorylation and activation of FGFR1, FRS2, MAPK3/ERK1, MAPK1/ERK2 and AKT1. Can induce angiogenesis (By similarity).By similarity2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Growth factor, Mitogen

Keywords - Biological processi

Angiogenesis, Differentiation

Keywords - Ligandi

Heparin-binding

Enzyme and pathway databases

ReactomeiR-BTA-109704. PI3K Cascade.
R-BTA-1257604. PIP3 activates AKT signaling.
R-BTA-190322. FGFR4 ligand binding and activation.
R-BTA-190370. FGFR1b ligand binding and activation.
R-BTA-190371. FGFR3b ligand binding and activation.
R-BTA-190372. FGFR3c ligand binding and activation.
R-BTA-190373. FGFR1c ligand binding and activation.
R-BTA-190375. FGFR2c ligand binding and activation.
R-BTA-190377. FGFR2b ligand binding and activation.
R-BTA-5654219. Phospholipase C-mediated cascade: FGFR1.
R-BTA-5654221. Phospholipase C-mediated cascade, FGFR2.
R-BTA-5654227. Phospholipase C-mediated cascade, FGFR3.
R-BTA-5654228. Phospholipase C-mediated cascade, FGFR4.
R-BTA-5654687. Downstream signaling of activated FGFR1.
R-BTA-5654688. SHC-mediated cascade:FGFR1.
R-BTA-5654689. PI-3K cascade:FGFR1.
R-BTA-5654693. FRS-mediated FGFR1 signaling.
R-BTA-5654695. PI-3K cascade:FGFR2.
R-BTA-5654699. SHC-mediated cascade:FGFR2.
R-BTA-5654700. FRS-mediated FGFR2 signaling.
R-BTA-5654704. SHC-mediated cascade:FGFR3.
R-BTA-5654706. FRS-mediated FGFR3 signaling.
R-BTA-5654710. PI-3K cascade:FGFR3.
R-BTA-5654712. FRS-mediated FGFR4 signaling.
R-BTA-5654719. SHC-mediated cascade:FGFR4.
R-BTA-5654720. PI-3K cascade:FGFR4.
R-BTA-5654726. Negative regulation of FGFR1 signaling.
R-BTA-5654727. Negative regulation of FGFR2 signaling.
R-BTA-5654732. Negative regulation of FGFR3 signaling.
R-BTA-5654733. Negative regulation of FGFR4 signaling.
R-BTA-5673001. RAF/MAP kinase cascade.
R-BTA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Fibroblast growth factor 1
Short name:
FGF-1
Alternative name(s):
Acidic eye-derived growth factor II
Short name:
EDGF II
Acidic fibroblast growth factor
Short name:
aFGF
Endothelial cell growth factor
Short name:
ECGF
Heparin-binding growth factor 1
Short name:
HBGF-1
Prostatropin
Cleaved into the following 2 chains:
Gene namesi
Name:FGF1
Synonyms:AFGF, FGFA, HBGF-1
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 7

Subcellular locationi

  • Secreted
  • Cytoplasm By similarity
  • Cytoplasmcell cortex By similarity
  • Cytoplasmcytosol
  • Nucleus

  • Note: Lacks a cleavable signal sequence. Within the cytoplasm, it is transported to the cell membrane and then secreted by a non-classical pathway that requires Cu2+ ions and S100A13. Secreted in a complex with SYT1. Binding of exogenous FGF1 to FGFR facilitates endocytosis followed by translocation of FGF1 across endosomal membrane into the cytosol. Nuclear import from the cytosol requires the classical nuclear import machinery, involving proteins KPNA1 and KPNB1, as well as LRRC59 (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved2 Publications
Chaini2 – 155154Endothelial cell growth factor betaPRO_0000008904Add
BLAST
Chaini16 – 155140Fibroblast growth factor 1PRO_0000008905Add
BLAST
Chaini22 – 155134Endothelial cell growth factor alphaPRO_0000008906Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine1 Publication

Post-translational modificationi

In the nucleus, phosphorylated by PKC/PRKCD.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP03968.

Expressioni

Gene expression databases

BgeeiENSBTAG00000005198.

Interactioni

Subunit structurei

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. Found in a complex with FGFBP1, FGF1 and FGF2. Interacts with FGFBP1. Part of a Cu2+-dependent multiprotein aggregate containing FGF1, S100A13 and SYT1. Interacts with S100A13. Interacts with FGFBP1 (By similarity). Interacts with LRRC59 (By similarity). Interacts with CSNKA, CSNKB and FIBP (By similarity). While binding with LRRC59, CSNKA and FIBP seem mutually exclusive, CSNKB and FIBP may cooperatively interact with FGF1 (By similarity). Interacts with SYT1 (PubMed:9712834). Forms a ternary complex with FGFR1 and ITGAV:ITGB3 and induces the recruitment of PTPN11 to the complex (By similarity).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
FGFR2P218022EBI-6358090,EBI-1028658From a different organism.
FGFR2P21802-32EBI-6358090,EBI-6354683From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi158520. 1 interaction.
IntActiP03968. 3 interactions.
STRINGi9913.ENSBTAP00000040651.

Structurei

Secondary structure

1
155
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi27 – 315Combined sources
Turni32 – 343Combined sources
Beta strandi37 – 404Combined sources
Beta strandi46 – 505Combined sources
Helixi55 – 573Combined sources
Beta strandi59 – 613Combined sources
Beta strandi65 – 673Combined sources
Beta strandi71 – 766Combined sources
Beta strandi79 – 824Combined sources
Beta strandi86 – 938Combined sources
Helixi96 – 983Combined sources
Beta strandi99 – 1046Combined sources
Beta strandi106 – 1083Combined sources
Beta strandi113 – 1153Combined sources
Turni116 – 1216Combined sources
Beta strandi130 – 1323Combined sources
Helixi135 – 1373Combined sources
Helixi143 – 1453Combined sources
Beta strandi147 – 1504Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AFCX-ray2.70A/B/C/D/E/F/G/H16-155[»]
1BARX-ray2.70A/B16-155[»]
ProteinModelPortaliP03968.
SMRiP03968. Positions 5-155.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03968.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni24 – 285Heparin-bindingSequence analysis
Regioni113 – 1164Heparin-bindingSequence analysis

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi24 – 274Nuclear localization signalBy similarity

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3885. Eukaryota.
ENOG4111IPH. LUCA.
GeneTreeiENSGT00730000110923.
HOGENOMiHOG000236341.
HOVERGENiHBG007580.
InParanoidiP03968.
KOiK18496.
OMAiLGPRTHY.
OrthoDBiEOG091G0NAY.
TreeFamiTF317805.

Family and domain databases

InterProiIPR008996. Cytokine_IL1-like.
IPR028210. FGF1.
IPR002209. Fibroblast_GF_fam.
IPR028142. IL-1_fam/FGF_fam.
[Graphical view]
PANTHERiPTHR11486. PTHR11486. 1 hit.
PTHR11486:SF86. PTHR11486:SF86. 1 hit.
PfamiPF00167. FGF. 1 hit.
[Graphical view]
PRINTSiPR00263. HBGFFGF.
PR00262. IL1HBGF.
SMARTiSM00442. FGF. 1 hit.
[Graphical view]
SUPFAMiSSF50353. SSF50353. 1 hit.
PROSITEiPS00247. HBGF_FGF. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P03968-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEGETTTFT ALTEKFNLPL GNYKKPKLLY CSNGGYFLRI LPDGTVDGTK
60 70 80 90 100
DRSDQHIQLQ LCAESIGEVY IKSTETGQFL AMDTDGLLYG SQTPNEECLF
110 120 130 140 150
LERLEENHYN TYISKKHAEK HWFVGLKKNG RSKLGPRTHF GQKAILFLPL

PVSSD
Length:155
Mass (Da):17,493
Last modified:July 1, 1989 - v2
Checksum:iF636641F189F9BFD
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X13221 mRNA. Translation: CAA31610.1.
X14032 mRNA. Translation: CAA32192.1.
M35608 mRNA. Translation: AAA30517.1.
BC103225 mRNA. Translation: AAI03226.1.
M13439 Genomic DNA. Translation: AAA30516.1.
X66446 mRNA. Translation: CAA47063.1.
M97660 mRNA. Translation: AAA30563.1.
M97661 mRNA. Translation: AAA30564.1.
PIRiJH0613. GKBOA.
RefSeqiNP_001300935.1. NM_001314006.1.
NP_776480.1. NM_174055.3.
XP_015327761.1. XM_015472275.1.
XP_015327762.1. XM_015472276.1.
XP_015327763.1. XM_015472277.1.
UniGeneiBt.5038.

Genome annotation databases

EnsembliENSBTAT00000043056; ENSBTAP00000040651; ENSBTAG00000005198.
GeneIDi281160.
KEGGibta:281160.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X13221 mRNA. Translation: CAA31610.1.
X14032 mRNA. Translation: CAA32192.1.
M35608 mRNA. Translation: AAA30517.1.
BC103225 mRNA. Translation: AAI03226.1.
M13439 Genomic DNA. Translation: AAA30516.1.
X66446 mRNA. Translation: CAA47063.1.
M97660 mRNA. Translation: AAA30563.1.
M97661 mRNA. Translation: AAA30564.1.
PIRiJH0613. GKBOA.
RefSeqiNP_001300935.1. NM_001314006.1.
NP_776480.1. NM_174055.3.
XP_015327761.1. XM_015472275.1.
XP_015327762.1. XM_015472276.1.
XP_015327763.1. XM_015472277.1.
UniGeneiBt.5038.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AFCX-ray2.70A/B/C/D/E/F/G/H16-155[»]
1BARX-ray2.70A/B16-155[»]
ProteinModelPortaliP03968.
SMRiP03968. Positions 5-155.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi158520. 1 interaction.
IntActiP03968. 3 interactions.
STRINGi9913.ENSBTAP00000040651.

Proteomic databases

PaxDbiP03968.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000043056; ENSBTAP00000040651; ENSBTAG00000005198.
GeneIDi281160.
KEGGibta:281160.

Organism-specific databases

CTDi2246.

Phylogenomic databases

eggNOGiKOG3885. Eukaryota.
ENOG4111IPH. LUCA.
GeneTreeiENSGT00730000110923.
HOGENOMiHOG000236341.
HOVERGENiHBG007580.
InParanoidiP03968.
KOiK18496.
OMAiLGPRTHY.
OrthoDBiEOG091G0NAY.
TreeFamiTF317805.

Enzyme and pathway databases

ReactomeiR-BTA-109704. PI3K Cascade.
R-BTA-1257604. PIP3 activates AKT signaling.
R-BTA-190322. FGFR4 ligand binding and activation.
R-BTA-190370. FGFR1b ligand binding and activation.
R-BTA-190371. FGFR3b ligand binding and activation.
R-BTA-190372. FGFR3c ligand binding and activation.
R-BTA-190373. FGFR1c ligand binding and activation.
R-BTA-190375. FGFR2c ligand binding and activation.
R-BTA-190377. FGFR2b ligand binding and activation.
R-BTA-5654219. Phospholipase C-mediated cascade: FGFR1.
R-BTA-5654221. Phospholipase C-mediated cascade, FGFR2.
R-BTA-5654227. Phospholipase C-mediated cascade, FGFR3.
R-BTA-5654228. Phospholipase C-mediated cascade, FGFR4.
R-BTA-5654687. Downstream signaling of activated FGFR1.
R-BTA-5654688. SHC-mediated cascade:FGFR1.
R-BTA-5654689. PI-3K cascade:FGFR1.
R-BTA-5654693. FRS-mediated FGFR1 signaling.
R-BTA-5654695. PI-3K cascade:FGFR2.
R-BTA-5654699. SHC-mediated cascade:FGFR2.
R-BTA-5654700. FRS-mediated FGFR2 signaling.
R-BTA-5654704. SHC-mediated cascade:FGFR3.
R-BTA-5654706. FRS-mediated FGFR3 signaling.
R-BTA-5654710. PI-3K cascade:FGFR3.
R-BTA-5654712. FRS-mediated FGFR4 signaling.
R-BTA-5654719. SHC-mediated cascade:FGFR4.
R-BTA-5654720. PI-3K cascade:FGFR4.
R-BTA-5654726. Negative regulation of FGFR1 signaling.
R-BTA-5654727. Negative regulation of FGFR2 signaling.
R-BTA-5654732. Negative regulation of FGFR3 signaling.
R-BTA-5654733. Negative regulation of FGFR4 signaling.
R-BTA-5673001. RAF/MAP kinase cascade.
R-BTA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.

Miscellaneous databases

EvolutionaryTraceiP03968.

Gene expression databases

BgeeiENSBTAG00000005198.

Family and domain databases

InterProiIPR008996. Cytokine_IL1-like.
IPR028210. FGF1.
IPR002209. Fibroblast_GF_fam.
IPR028142. IL-1_fam/FGF_fam.
[Graphical view]
PANTHERiPTHR11486. PTHR11486. 1 hit.
PTHR11486:SF86. PTHR11486:SF86. 1 hit.
PfamiPF00167. FGF. 1 hit.
[Graphical view]
PRINTSiPR00263. HBGFFGF.
PR00262. IL1HBGF.
SMARTiSM00442. FGF. 1 hit.
[Graphical view]
SUPFAMiSSF50353. SSF50353. 1 hit.
PROSITEiPS00247. HBGF_FGF. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFGF1_BOVIN
AccessioniPrimary (citable) accession number: P03968
Secondary accession number(s): Q3ZBL8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 23, 1986
Last sequence update: July 1, 1989
Last modified: September 7, 2016
This is version 153 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

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 one 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.