Vascular endothelial growth factor A

Details

Name
Vascular endothelial growth factor A
Synonyms
  • Vascular permeability factor
  • VEGF
  • VEGF-A
  • VPF
Gene Name
VEGFA
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000325|Vascular endothelial growth factor A
MNFLLSWVHWSLALLLYLHHAKWSQAAPMAEGGGQNHHEVVKFMDVYQRSYCHPIETLVD
IFQEYPDEIEYIFKPSCVPLMRCGGCCNDEGLECVPTEESNITMQIMRIKPHQGQHIGEM
SFLQHNKCECRPKKDRARQEKKSVRGKGKGQKRKRKKSRYKSWSVYVGARCCLMPWSLPG
PHPCGPCSERRKHLFVQDPQTCKCSCKNTDSRCKARQLELNERTCRCDKPRR
Number of residues
232
Molecular Weight
27042.205
Theoretical pI
9.08
GO Classification
Functions
chemoattractant activity / cytokine activity / extracellular matrix binding / fibronectin binding / growth factor activity / heparin binding / identical protein binding / neuropilin binding / platelet-derived growth factor receptor binding / protein heterodimerization activity / protein homodimerization activity / receptor agonist activity / vascular endothelial growth factor receptor 1 binding / vascular endothelial growth factor receptor 2 binding / vascular endothelial growth factor receptor binding
Processes
activation of protein kinase activity / angiogenesis / artery morphogenesis / basophil chemotaxis / blood coagulation / branching morphogenesis of an epithelial tube / camera-type eye morphogenesis / cardiac muscle fiber development / cardiac vascular smooth muscle cell development / cell maturation / cell migration involved in sprouting angiogenesis / cellular response to hypoxia / cellular response to vascular endothelial growth factor stimulus / commissural neuron axon guidance / coronary artery morphogenesis / coronary vein morphogenesis / dopaminergic neuron differentiation / endothelial cell chemotaxis / epithelial cell differentiation / eye photoreceptor cell development / growth / heart morphogenesis / in utero embryonic development / induction of positive chemotaxis / kidney development / lactation / lung development / lymph vessel morphogenesis / macrophage differentiation / mammary gland alveolus development / mesoderm development / monocyte differentiation / negative regulation of apoptotic process / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / negative regulation of transcription from RNA polymerase II promoter / nervous system development / outflow tract morphogenesis / ovarian follicle development / patterning of blood vessels / platelet activation / platelet degranulation / positive chemotaxis / positive regulation of angiogenesis / positive regulation of axon extension involved in axon guidance / positive regulation of blood vessel endothelial cell migration / positive regulation of branching involved in ureteric bud morphogenesis / positive regulation of cell adhesion / positive regulation of cell division / positive regulation of cell migration / positive regulation of cell migration involved in sprouting angiogenesis / positive regulation of cell proliferation / positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway / positive regulation of cellular component movement / positive regulation of CREB transcription factor activity / positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway / positive regulation of endothelial cell migration / positive regulation of endothelial cell proliferation / positive regulation of epithelial cell proliferation / positive regulation of ERK1 and ERK2 cascade / positive regulation of focal adhesion assembly / positive regulation of gene expression / positive regulation of histone deacetylase activity / positive regulation of leukocyte migration / positive regulation of MAP kinase activity / positive regulation of mast cell chemotaxis / positive regulation of mesenchymal cell proliferation / positive regulation of neuroblast proliferation / positive regulation of p38MAPK cascade / positive regulation of peptidyl-serine phosphorylation / positive regulation of peptidyl-tyrosine autophosphorylation / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of positive chemotaxis / positive regulation of protein autophosphorylation / positive regulation of protein complex assembly / positive regulation of protein kinase C signaling / positive regulation of protein kinase D signaling / positive regulation of protein localization to early endosome / positive regulation of protein phosphorylation / positive regulation of receptor internalization / positive regulation of retinal ganglion cell axon guidance / positive regulation of transcription from RNA polymerase II promoter / positive regulation of transcription from RNA polymerase II promoter in response to hypoxia / positive regulation of vascular endothelial growth factor receptor signaling pathway / positive regulation of vascular permeability / post-embryonic camera-type eye development / primitive erythrocyte differentiation / regulation of cell shape / regulation of cGMP metabolic process / regulation of retinal ganglion cell axon guidance / regulation of transcription from RNA polymerase II promoter / regulation of transcription from RNA polymerase II promoter in response to hypoxia / response to hypoxia / surfactant homeostasis / tube formation / vascular endothelial growth factor receptor signaling pathway / vascular endothelial growth factor signaling pathway / vasculogenesis / VEGF-activated neuropilin signaling pathway
Components
cell surface / cytoplasm / extracellular region / extracellular space / membrane / platelet alpha granule lumen / proteinaceous extracellular matrix / secretory granule
General Function
Vascular endothelial growth factor receptor binding
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0021644|Vascular endothelial growth factor A (VEGFA)
CTGACGGACAGACAGACAGACACCGCCCCCAGCCCCAGCTACCACCTCCTCCCCGGCCGG
CGGCGGACAGTGGACGCGGCGGCGAGCCGCGGGCAGGGGCCGGAGCCCGCGCCCGGAGGC
GGGGTGGAGGGGGTCGGGGCTCGCGGCGTCGCACTGAAACTTTTCGTCCAACTTCTGGGC
TGTTCTCGCTTCGGAGGAGCCGTGGTCCGCGCGGGGGAAGCCGAGCCGAGCGGAGCCGCG
AGAAGTGCTAGCTCGGGCCGGGAGGAGCCGCAGCCGGAGGAGGGGGAGGAGGAAGAAGAG
AAGGAAGAGGAGAGGGGGCCGCAGTGGCGACTCGGCGCTCGGAAGCCGGGCTCATGGACG
GGTGAGGCGGCGGTGTGCGCAGACAGTGCTCCAGCCGCGCGCGCTCCCCAGGCCCTGGCC
CGGGCCTCGGGCCGGGGAGGAAGAGTAGCTCGCCGAGGCGCCGAGGAGAGCGGGCCGCCC
CACAGCCCGAGCCGGAGAGGGAGCGCGAGCCGCGCCGGCCCCGGTCGGGCCTCCGAAACC
ATGAACTTTCTGCTGTCTTGGGTGCATTGGAGCCTTGCCTTGCTGCTCTACCTCCACCAT
GCCAAGTGGTCCCAGGCTGCACCCATGGCAGAAGGAGGAGGGCAGAATCATCACGAAGTG
GTGAAGTTCATGGATGTCTATCAGCGCAGCTACTGCCATCCAATCGAGACCCTGGTGGAC
ATCTTCCAGGAGTACCCTGATGAGATCGAGTACATCTTCAAGCCATCCTGTGTGCCCCTG
ATGCGATGCGGGGGCTGCTGCAATGACGAGGGCCTGGAGTGTGTGCCCACTGAGGAGTCC
AACATCACCATGCAGATTATGCGGATCAAACCTCACCAAGGCCAGCACATAGGAGAGATG
AGCTTCCTACAGCACAACAAATGTGAATGCAGACCAAAGAAAGATAGAGCAAGACAAGAA
AAAAAATCAGTTCGAGGAAAGGGAAAGGGGCAAAAACGAAAGCGCAAGAAATCCCGGTAT
AAGTCCTGGAGCGTGTACGTTGGTGCCCGCTGCTGTCTAATGCCCTGGAGCCTCCCTGGC
CCCCATCCCTGTGGGCCTTGCTCAGAGCGGAGAAAGCATTTGTTTGTACAAGATCCGCAG
ACGTGTAAATGTTCCTGCAAAAACACAGACTCGCGTTGCAAGGCGAGGCAGCTTGAGTTA
AACGAACGTACTTGCAGATGTGACAAGCCGAGGCGGTGA
Chromosome Location
6
Locus
6p12
External Identifiers
ResourceLink
UniProtKB IDP15692
UniProtKB Entry NameVEGFA_HUMAN
GenBank Protein ID181971
GenBank Gene IDM32977
GenAtlas IDVEGF
HGNC IDHGNC:12680
General References
  1. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N: Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989 Dec 8;246(4935):1306-9. [Article]
  2. Keck PJ, Hauser SD, Krivi G, Sanzo K, Warren T, Feder J, Connolly DT: Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science. 1989 Dec 8;246(4935):1309-12. [Article]
  3. Tischer E, Mitchell R, Hartman T, Silva M, Gospodarowicz D, Fiddes JC, Abraham JA: The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem. 1991 Jun 25;266(18):11947-54. [Article]
  4. Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW: The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol. 1991 Dec;5(12):1806-14. [Article]
  5. Weindel K, Marme D, Weich HA: AIDS-associated Kaposi's sarcoma cells in culture express vascular endothelial growth factor. Biochem Biophys Res Commun. 1992 Mar 31;183(3):1167-74. [Article]
  6. Poltorak Z, Cohen T, Sivan R, Kandelis Y, Spira G, Vlodavsky I, Keshet E, Neufeld G: VEGF145, a secreted vascular endothelial growth factor isoform that binds to extracellular matrix. J Biol Chem. 1997 Mar 14;272(11):7151-8. [Article]
  7. Lei J, Jiang A, Pei D: Identification and characterization of a new splicing variant of vascular endothelial growth factor: VEGF183. Biochim Biophys Acta. 1998 Dec 22;1443(3):400-6. [Article]
  8. Claffey KP, Shih SC, Mullen A, Dziennis S, Cusick JL, Abrams KR, Lee SW, Detmar M: Identification of a human VPF/VEGF 3' untranslated region mediating hypoxia-induced mRNA stability. Mol Biol Cell. 1998 Feb;9(2):469-81. [Article]
  9. Whittle C, Gillespie K, Harrison R, Mathieson PW, Harper SJ: Heterogeneous vascular endothelial growth factor (VEGF) isoform mRNA and receptor mRNA expression in human glomeruli, and the identification of VEGF148 mRNA, a novel truncated splice variant. Clin Sci (Lond). 1999 Sep;97(3):303-12. [Article]
  10. Bates DO, Cui TG, Doughty JM, Winkler M, Sugiono M, Shields JD, Peat D, Gillatt D, Harper SJ: VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, is down-regulated in renal cell carcinoma. Cancer Res. 2002 Jul 15;62(14):4123-31. [Article]
  11. Goshima N, Kawamura Y, Fukumoto A, Miura A, Honma R, Satoh R, Wakamatsu A, Yamamoto J, Kimura K, Nishikawa T, Andoh T, Iida Y, Ishikawa K, Ito E, Kagawa N, Kaminaga C, Kanehori K, Kawakami B, Kenmochi K, Kimura R, Kobayashi M, Kuroita T, Kuwayama H, Maruyama Y, Matsuo K, Minami K, Mitsubori M, Mori M, Morishita R, Murase A, Nishikawa A, Nishikawa S, Okamoto T, Sakagami N, Sakamoto Y, Sasaki Y, Seki T, Sono S, Sugiyama A, Sumiya T, Takayama T, Takayama Y, Takeda H, Togashi T, Yahata K, Yamada H, Yanagisawa Y, Endo Y, Imamoto F, Kisu Y, Tanaka S, Isogai T, Imai J, Watanabe S, Nomura N: Human protein factory for converting the transcriptome into an in vitro-expressed proteome,. Nat Methods. 2008 Dec;5(12):1011-7. [Article]
  12. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [Article]
  13. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  14. Fiebich BL, Jager B, Schollmann C, Weindel K, Wilting J, Kochs G, Marme D, Hug H, Weich HA: Synthesis and assembly of functionally active human vascular endothelial growth factor homodimers in insect cells. Eur J Biochem. 1993 Jan 15;211(1-2):19-26. [Article]
  15. Zhang Z, Henzel WJ: Signal peptide prediction based on analysis of experimentally verified cleavage sites. Protein Sci. 2004 Oct;13(10):2819-24. Epub 2004 Aug 31. [Article]
  16. Connolly DT, Olander JV, Heuvelman D, Nelson R, Monsell R, Siegel N, Haymore BL, Leimgruber R, Feder J: Human vascular permeability factor. Isolation from U937 cells. J Biol Chem. 1989 Nov 25;264(33):20017-24. [Article]
  17. Jingjing L, Xue Y, Agarwal N, Roque RS: Human Muller cells express VEGF183, a novel spliced variant of vascular endothelial growth factor. Invest Ophthalmol Vis Sci. 1999 Mar;40(3):752-9. [Article]
  18. Tee MK, Jaffe RB: A precursor form of vascular endothelial growth factor arises by initiation from an upstream in-frame CUG codon. Biochem J. 2001 Oct 1;359(Pt 1):219-26. [Article]
  19. Murphy JF, Fitzgerald DJ: Vascular endothelial growth factor induces cyclooxygenase-dependent proliferation of endothelial cells via the VEGF-2 receptor. FASEB J. 2001 Jul;15(9):1667-9. [Article]
  20. Huez I, Bornes S, Bresson D, Creancier L, Prats H: New vascular endothelial growth factor isoform generated by internal ribosome entry site-driven CUG translation initiation. Mol Endocrinol. 2001 Dec;15(12):2197-210. [Article]
  21. Awata T, Inoue K, Kurihara S, Ohkubo T, Watanabe M, Inukai K, Inoue I, Katayama S: A common polymorphism in the 5'-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes. 2002 May;51(5):1635-9. [Article]
  22. Woolard J, Wang WY, Bevan HS, Qiu Y, Morbidelli L, Pritchard-Jones RO, Cui TG, Sugiono M, Waine E, Perrin R, Foster R, Digby-Bell J, Shields JD, Whittles CE, Mushens RE, Gillatt DA, Ziche M, Harper SJ, Bates DO: VEGF165b, an inhibitory vascular endothelial growth factor splice variant: mechanism of action, in vivo effect on angiogenesis and endogenous protein expression. Cancer Res. 2004 Nov 1;64(21):7822-35. [Article]
  23. Bornes S, Boulard M, Hieblot C, Zanibellato C, Iacovoni JS, Prats H, Touriol C: Control of the vascular endothelial growth factor internal ribosome entry site (IRES) activity and translation initiation by alternatively spliced coding sequences. J Biol Chem. 2004 Apr 30;279(18):18717-26. Epub 2004 Feb 5. [Article]
  24. Rosenbaum-Dekel Y, Fuchs A, Yakirevich E, Azriel A, Mazareb S, Resnick MB, Levi BZ: Nuclear localization of long-VEGF is associated with hypoxia and tumor angiogenesis. Biochem Biophys Res Commun. 2005 Jun 24;332(1):271-8. [Article]
  25. Dixelius J, Olsson AK, Thulin A, Lee C, Johansson I, Claesson-Welsh L: Minimal active domain and mechanism of action of the angiogenesis inhibitor histidine-rich glycoprotein. Cancer Res. 2006 Feb 15;66(4):2089-97. [Article]
  26. Shan B, Gerez J, Haedo M, Fuertes M, Theodoropoulou M, Buchfelder M, Losa M, Stalla GK, Arzt E, Renner U: RSUME is implicated in HIF-1-induced VEGF-A production in pituitary tumour cells. Endocr Relat Cancer. 2012 Jan 9;19(1):13-27. doi: 10.1530/ERC-11-0211. Print 2012 Feb. [Article]
  27. Muller YA, Li B, Christinger HW, Wells JA, Cunningham BC, de Vos AM: Vascular endothelial growth factor: crystal structure and functional mapping of the kinase domain receptor binding site. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7192-7. [Article]
  28. Fairbrother WJ, Champe MA, Christinger HW, Keyt BA, Starovasnik MA: 1H, 13C, and 15N backbone assignment and secondary structure of the receptor-binding domain of vascular endothelial growth factor. Protein Sci. 1997 Oct;6(10):2250-60. [Article]
  29. Muller YA, Christinger HW, Keyt BA, de Vos AM: The crystal structure of vascular endothelial growth factor (VEGF) refined to 1.93 A resolution: multiple copy flexibility and receptor binding. Structure. 1997 Oct 15;5(10):1325-38. [Article]
  30. Wiesmann C, Christinger HW, Cochran AG, Cunningham BC, Fairbrother WJ, Keenan CJ, Meng G, de Vos AM: Crystal structure of the complex between VEGF and a receptor-blocking peptide. Biochemistry. 1998 Dec 22;37(51):17765-72. [Article]
  31. Fairbrother WJ, Champe MA, Christinger HW, Keyt BA, Starovasnik MA: Solution structure of the heparin-binding domain of vascular endothelial growth factor. Structure. 1998 May 15;6(5):637-48. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01270RanibizumabapprovedyesantibodyDetails
DB01017Minocyclineapproved, investigationalunknowninhibitorDetails
DB01120Gliclazideapprovedunknownother/unknownDetails
DB01136Carvedilolapproved, investigationalunknownotherDetails
DB03088Pidolic acidapproved, investigationalunknownDetails
DB00112Bevacizumabapproved, investigationalyesDetails
DB04895Pegaptanibapproved, investigationalyesantagonistDetails
DB05294VandetanibapprovedunknowninhibitorDetails
DB05434ABT-510investigationalunknownDetails
DB05890VeglininvestigationalunknownDetails
DB05932DenibulininvestigationalunknownDetails
DB05969SNS-032investigationalunknownDetails
DB06642BevasiranibinvestigationalunknownDetails
DB06779DalteparinapprovedyesinhibitorDetails
DB08885AfliberceptapprovedyesinhibitorbinderDetails
DB09301Chondroitin sulfateapproved, investigational, nutraceuticalunknownDetails
DB10772Foreskin keratinocyte (neonatal)approvedyesagonistDetails
DB14864Brolucizumabapproved, investigationalyesinhibitorDetails
DB15303Faricimabapproved, investigationalyesantagonistDetails
DB12317VanucizumabinvestigationalunknownregulatorDetails