UniProt functional annotation for P15692



	UniProt functional annotation for P15692

UniProt code: P15692.

Organism: Homo sapiens (Human).

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

Function: Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth. Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development (By similarity). {ECO:0000250|UniProtKB:Q00731, ECO:0000269|PubMed:11427521, ECO:0000269|PubMed:16489009, ECO:0000269|PubMed:25825981}.

Subunit: Homodimer; disulfide-linked (By similarity). Also found as heterodimer with PGF (By similarity). Interacts with NRP1 (PubMed:26503042). Interacts with isoform 2 of BSG (PubMed:25825981). {ECO:0000250|UniProtKB:P16612, ECO:0000269|PubMed:25825981, ECO:0000269|PubMed:26503042}.

Subcellular location: Secreted {ECO:0000269|PubMed:11563986, ECO:0000269|PubMed:11731620, ECO:0000269|PubMed:15896327}. Note=VEGF121 is acidic and freely secreted. VEGF165 is more basic, has heparin- binding properties and, although a significant proportion remains cell- associated, most is freely secreted. VEGF189 is very basic, it is cell- associated after secretion and is bound avidly by heparin and the extracellular matrix, although it may be released as a soluble form by heparin, heparinase or plasmin.

Tissue specificity: Isoform VEGF189, isoform VEGF165 and isoform VEGF121 are widely expressed. Isoform VEGF206 and isoform VEGF145 are not widely expressed. A higher level expression seen in pituitary tumors as compared to the pituitary gland. {ECO:0000269|PubMed:22009797}.

Induction: By hypoxia. Regulated by growth factors, cytokines, gonadotropins, nitric oxide, hypoglycemia and oncogenic mutations. {ECO:0000269|PubMed:22009797}.

Disease: Microvascular complications of diabetes 1 (MVCD1) [MIM:603933]: Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. {ECO:0000269|PubMed:11978667}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Miscellaneous: [Isoform L-VEGF165]: Produced by alternative promoter usage and alternative initiation. Starts at an alternative upstream CUG codon. Post-translationally processed to produce the secreted VEGF peptide and a N-terminal peptide N-VEGF. The unprocessed protein and the N-VEGF peptide may localize to the nucleus (PubMed:15896327), the endoplasmic reticulum and the Golgi (PubMed:11731620) or the extracellular matrix (PubMed:11563986). {ECO:0000305|PubMed:11563986, ECO:0000305|PubMed:11731620, ECO:0000305|PubMed:15896327}.

Miscellaneous: [Isoform L-VEGF121]: Produced by alternative promoter usage and alternative initiation. Starts at an alternative upstream CUG codon. Post-translationally processed to produce the secreted VEGF peptide and a N-terminal peptide N-VEGF. The unprocessed protein and the N-VEGF peptide may localize to the nucleus (PubMed:15896327), the endoplasmic reticulum and the Golgi (PubMed:11731620) or the extracellular matrix (PubMed:11563986). {ECO:0000305|PubMed:11563986, ECO:0000305|PubMed:11731620, ECO:0000305|PubMed:15896327}.

Miscellaneous: [Isoform L-VEGF189]: Produced by alternative promoter usage and alternative initiation. Starts at an alternative upstream CUG codon. Post-translationally processed to produce the secreted VEGF peptide and a N-terminal peptide N-VEGF. The unprocessed protein and the N-VEGF peptide may localize to the nucleus (PubMed:15896327), the endoplasmic reticulum and the Golgi (PubMed:11731620) or the extracellular matrix (PubMed:11563986). {ECO:0000305|PubMed:11563986, ECO:0000305|PubMed:11731620, ECO:0000305|PubMed:15896327}.

Miscellaneous: [Isoform L-VEGF206]: Produced by alternative promoter usage and alternative initiation. Starts at an alternative upstream CUG codon. {ECO:0000305}.

Miscellaneous: [Isoform 15]: Starts at an alternative upstream CUG codon. {ECO:0000305}.

Miscellaneous: [Isoform 16]: Starts at an alternative upstream CUG codon. {ECO:0000305}.

Miscellaneous: [Isoform 17]: Starts at an alternative upstream CUG codon. {ECO:0000305}.

Miscellaneous: [Isoform 18]: Starts at an alternative upstream CUG codon. {ECO:0000305}.

Similarity: Belongs to the PDGF/VEGF growth factor family. {ECO:0000305}.

Sequence caution: Sequence=AAC63102.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAC63143.1; 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:		Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth. Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development (By similarity). {ECO:0000250\|UniProtKB:Q00731, ECO:0000269\|PubMed:11427521, ECO:0000269\|PubMed:16489009, ECO:0000269\|PubMed:25825981}.


Subunit:		Homodimer; disulfide-linked (By similarity). Also found as heterodimer with PGF (By similarity). Interacts with NRP1 (PubMed:26503042). Interacts with isoform 2 of BSG (PubMed:25825981). {ECO:0000250\|UniProtKB:P16612, ECO:0000269\|PubMed:25825981, ECO:0000269\|PubMed:26503042}.
Subcellular location:		Secreted {ECO:0000269\|PubMed:11563986, ECO:0000269\|PubMed:11731620, ECO:0000269\|PubMed:15896327}. Note=VEGF121 is acidic and freely secreted. VEGF165 is more basic, has heparin- binding properties and, although a significant proportion remains cell- associated, most is freely secreted. VEGF189 is very basic, it is cell- associated after secretion and is bound avidly by heparin and the extracellular matrix, although it may be released as a soluble form by heparin, heparinase or plasmin.
Tissue specificity:		Isoform VEGF189, isoform VEGF165 and isoform VEGF121 are widely expressed. Isoform VEGF206 and isoform VEGF145 are not widely expressed. A higher level expression seen in pituitary tumors as compared to the pituitary gland. {ECO:0000269\|PubMed:22009797}.
Induction:		By hypoxia. Regulated by growth factors, cytokines, gonadotropins, nitric oxide, hypoglycemia and oncogenic mutations. {ECO:0000269\|PubMed:22009797}.
Disease:		Microvascular complications of diabetes 1 (MVCD1) [MIM:603933]: Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. {ECO:0000269\|PubMed:11978667}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform L-VEGF165]: Produced by alternative promoter usage and alternative initiation. Starts at an alternative upstream CUG codon. Post-translationally processed to produce the secreted VEGF peptide and a N-terminal peptide N-VEGF. The unprocessed protein and the N-VEGF peptide may localize to the nucleus (PubMed:15896327), the endoplasmic reticulum and the Golgi (PubMed:11731620) or the extracellular matrix (PubMed:11563986). {ECO:0000305\|PubMed:11563986, ECO:0000305\|PubMed:11731620, ECO:0000305\|PubMed:15896327}.
Miscellaneous:		[Isoform L-VEGF121]: Produced by alternative promoter usage and alternative initiation. Starts at an alternative upstream CUG codon. Post-translationally processed to produce the secreted VEGF peptide and a N-terminal peptide N-VEGF. The unprocessed protein and the N-VEGF peptide may localize to the nucleus (PubMed:15896327), the endoplasmic reticulum and the Golgi (PubMed:11731620) or the extracellular matrix (PubMed:11563986). {ECO:0000305\|PubMed:11563986, ECO:0000305\|PubMed:11731620, ECO:0000305\|PubMed:15896327}.
Miscellaneous:		[Isoform L-VEGF189]: Produced by alternative promoter usage and alternative initiation. Starts at an alternative upstream CUG codon. Post-translationally processed to produce the secreted VEGF peptide and a N-terminal peptide N-VEGF. The unprocessed protein and the N-VEGF peptide may localize to the nucleus (PubMed:15896327), the endoplasmic reticulum and the Golgi (PubMed:11731620) or the extracellular matrix (PubMed:11563986). {ECO:0000305\|PubMed:11563986, ECO:0000305\|PubMed:11731620, ECO:0000305\|PubMed:15896327}.
Miscellaneous:		[Isoform L-VEGF206]: Produced by alternative promoter usage and alternative initiation. Starts at an alternative upstream CUG codon. {ECO:0000305}.
Miscellaneous:		[Isoform 15]: Starts at an alternative upstream CUG codon. {ECO:0000305}.
Miscellaneous:		[Isoform 16]: Starts at an alternative upstream CUG codon. {ECO:0000305}.
Miscellaneous:		[Isoform 17]: Starts at an alternative upstream CUG codon. {ECO:0000305}.
Miscellaneous:		[Isoform 18]: Starts at an alternative upstream CUG codon. {ECO:0000305}.
Similarity:		Belongs to the PDGF/VEGF growth factor family. {ECO:0000305}.
Sequence caution:		Sequence=AAC63102.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAC63143.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};