UniProt functional annotation for P09038



	UniProt functional annotation for P09038

UniProt code: P09038.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Acts as a ligand for FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:8663044). Also acts as an integrin ligand which is required for FGF2 signaling (PubMed:28302677). Binds to integrin ITGAV:ITGB3 (PubMed:28302677). Plays an important role in the regulation of cell survival, cell division, cell differentiation and cell migration (PubMed:8663044, PubMed:28302677). Functions as a potent mitogen in vitro (PubMed:1721615, PubMed:3964259, PubMed:3732516). Can induce angiogenesis (PubMed:23469107, PubMed:28302677). Mediates phosphorylation of ERK1/2 and thereby promotes retinal lens fiber differentiation (PubMed:29501879). {ECO:0000269|PubMed:1721615, ECO:0000269|PubMed:29501879, ECO:0000269|PubMed:3732516, ECO:0000269|PubMed:3964259}.

Biophysicochemical properties: pH dependence: Retains almost half of its activity after treatment at pH 2.0 for 3 hours at 20 degrees Celsius. {ECO:0000269|PubMed:1721615}; Temperature dependence: Inactivated after 3 minutes at 60 degrees Celsius or 1 minute at 80 degrees Celsius. {ECO:0000269|PubMed:1721615};

Subunit: 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. Interacts with CSPG4, FGFBP1 and TEC. Found in a complex with FGFBP1, FGF1 and FGF2. Interacts with FGFBP3 (PubMed:18669637). Interacts with integrin ITGAV:ITGB3; the interaction is required for FGF2 signaling (PubMed:28302677). Interacts with SNORC (via the extracellular domain) (By similarity). Interacts with glypican GPC3 (By similarity). {ECO:0000250|UniProtKB:P13109, ECO:0000250|UniProtKB:P15655, ECO:0000269|PubMed:10358027, ECO:0000269|PubMed:11390973, ECO:0000269|PubMed:11509569, ECO:0000269|PubMed:11964394, ECO:0000269|PubMed:16257968, ECO:0000269|PubMed:18669637, ECO:0000269|PubMed:1885605, ECO:0000269|PubMed:20230531, ECO:0000269|PubMed:28302677, ECO:0000269|PubMed:8663044}.

Subcellular location: Secreted {ECO:0000269|PubMed:20230531}. Nucleus {ECO:0000269|PubMed:22321063}. Note=Exported from cells by an endoplasmic reticulum (ER)/Golgi-independent mechanism. Unconventional secretion of FGF2 occurs by direct translocation across the plasma membrane (PubMed:20230531). Binding of exogenous FGF2 to FGFR facilitates endocytosis followed by translocation of FGF2 across endosomal membrane into the cytosol (PubMed:22321063). Nuclear import from the cytosol requires the classical nuclear import machinery, involving proteins KPNA1 and KPNB1, as well as CEP57 (PubMed:22321063). {ECO:0000269|PubMed:20230531, ECO:0000269|PubMed:22321063}.

Tissue specificity: Expressed in granulosa and cumulus cells. Expressed in hepatocellular carcinoma cells, but not in non-cancerous liver tissue. {ECO:0000269|PubMed:1417798, ECO:0000269|PubMed:1721615}.

Ptm: Phosphorylation at Tyr-215 regulates FGF2 unconventional secretion. {ECO:0000269|PubMed:20230531}.

Ptm: Several N-termini starting at positions 94, 125, 126, 132, 143 and 162 have been identified by direct sequencing.

Miscellaneous: This protein binds heparin more strongly than does aFGF.

Miscellaneous: [Isoform 1]: Starts at an alternative CUG codon.

Miscellaneous: [Isoform 2]: Starts at an alternative CUG codon. {ECO:0000305}.

Miscellaneous: [Isoform 4]: Starts at an alternative CUG codon. {ECO:0000305}.

Similarity: Belongs to the heparin-binding growth factors family. {ECO:0000305}.

Sequence caution: Sequence=AAA52448.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAB21432.2; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAB21432.2; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305}; Sequence=ABO43041.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=ABO43041.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305}; Sequence=CAA28027.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=CAA28027.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305}; Sequence=CAA73868.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=CAA73868.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305}; Sequence=EAX05222.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=EAX05222.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Acts as a ligand for FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:8663044). Also acts as an integrin ligand which is required for FGF2 signaling (PubMed:28302677). Binds to integrin ITGAV:ITGB3 (PubMed:28302677). Plays an important role in the regulation of cell survival, cell division, cell differentiation and cell migration (PubMed:8663044, PubMed:28302677). Functions as a potent mitogen in vitro (PubMed:1721615, PubMed:3964259, PubMed:3732516). Can induce angiogenesis (PubMed:23469107, PubMed:28302677). Mediates phosphorylation of ERK1/2 and thereby promotes retinal lens fiber differentiation (PubMed:29501879). {ECO:0000269\|PubMed:1721615, ECO:0000269\|PubMed:29501879, ECO:0000269\|PubMed:3732516, ECO:0000269\|PubMed:3964259}.


Biophysicochemical properties:		pH dependence: Retains almost half of its activity after treatment at pH 2.0 for 3 hours at 20 degrees Celsius. {ECO:0000269\|PubMed:1721615}; Temperature dependence: Inactivated after 3 minutes at 60 degrees Celsius or 1 minute at 80 degrees Celsius. {ECO:0000269\|PubMed:1721615};
Subunit:		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. Interacts with CSPG4, FGFBP1 and TEC. Found in a complex with FGFBP1, FGF1 and FGF2. Interacts with FGFBP3 (PubMed:18669637). Interacts with integrin ITGAV:ITGB3; the interaction is required for FGF2 signaling (PubMed:28302677). Interacts with SNORC (via the extracellular domain) (By similarity). Interacts with glypican GPC3 (By similarity). {ECO:0000250\|UniProtKB:P13109, ECO:0000250\|UniProtKB:P15655, ECO:0000269\|PubMed:10358027, ECO:0000269\|PubMed:11390973, ECO:0000269\|PubMed:11509569, ECO:0000269\|PubMed:11964394, ECO:0000269\|PubMed:16257968, ECO:0000269\|PubMed:18669637, ECO:0000269\|PubMed:1885605, ECO:0000269\|PubMed:20230531, ECO:0000269\|PubMed:28302677, ECO:0000269\|PubMed:8663044}.
Subcellular location:		Secreted {ECO:0000269\|PubMed:20230531}. Nucleus {ECO:0000269\|PubMed:22321063}. Note=Exported from cells by an endoplasmic reticulum (ER)/Golgi-independent mechanism. Unconventional secretion of FGF2 occurs by direct translocation across the plasma membrane (PubMed:20230531). Binding of exogenous FGF2 to FGFR facilitates endocytosis followed by translocation of FGF2 across endosomal membrane into the cytosol (PubMed:22321063). Nuclear import from the cytosol requires the classical nuclear import machinery, involving proteins KPNA1 and KPNB1, as well as CEP57 (PubMed:22321063). {ECO:0000269\|PubMed:20230531, ECO:0000269\|PubMed:22321063}.
Tissue specificity:		Expressed in granulosa and cumulus cells. Expressed in hepatocellular carcinoma cells, but not in non-cancerous liver tissue. {ECO:0000269\|PubMed:1417798, ECO:0000269\|PubMed:1721615}.
Ptm:		Phosphorylation at Tyr-215 regulates FGF2 unconventional secretion. {ECO:0000269\|PubMed:20230531}.
Ptm:		Several N-termini starting at positions 94, 125, 126, 132, 143 and 162 have been identified by direct sequencing.
Miscellaneous:		This protein binds heparin more strongly than does aFGF.
Miscellaneous:		[Isoform 1]: Starts at an alternative CUG codon.
Miscellaneous:		[Isoform 2]: Starts at an alternative CUG codon. {ECO:0000305}.
Miscellaneous:		[Isoform 4]: Starts at an alternative CUG codon. {ECO:0000305}.
Similarity:		Belongs to the heparin-binding growth factors family. {ECO:0000305}.
Sequence caution:		Sequence=AAA52448.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAB21432.2; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAB21432.2; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305}; Sequence=ABO43041.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=ABO43041.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305}; Sequence=CAA28027.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=CAA28027.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305}; Sequence=CAA73868.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=CAA73868.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305}; Sequence=EAX05222.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=EAX05222.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};