ID VEGFA_HUMAN Reviewed; 232 AA. AC P15692; B5BU86; H0Y2S8; H0Y407; H0Y414; H0Y462; H0Y8N2; H3BLW7; AC O60720; O75875; Q074Z4; Q16889; Q5UB46; Q6P0P5; Q96KJ0; Q96L82; AC Q96NW5; Q9H1W8; Q9H1W9; Q9UH58; Q9UL23; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 16-NOV-2001, sequence version 2. DT 11-NOV-2015, entry version 205. DE RecName: Full=Vascular endothelial growth factor A; DE Short=VEGF-A; DE AltName: Full=Vascular permeability factor; DE Short=VPF; DE Flags: Precursor; GN Name=VEGFA; Synonyms=VEGF; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS VEGF189 AND VEGF165). RX PubMed=2479986; DOI=10.1126/science.2479986; RA Leung D.W., Cachianes G., Kuang W.-J., Goeddel D.V., Ferrara N.; RT "Vascular endothelial growth factor is a secreted angiogenic RT mitogen."; RL Science 246:1306-1309(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF189), AND PARTIAL PROTEIN RP SEQUENCE. RX PubMed=2479987; DOI=10.1126/science.2479987; RA Keck P.J., Hauser S.D., Krivi G., Sanzo K., Warren T., Feder J., RA Connolly D.T.; RT "Vascular permeability factor, an endothelial cell mitogen related to RT PDGF."; RL Science 246:1309-1312(1989). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM VEGF189). RX PubMed=1711045; RA Tischer E., Mitchell R., Hartman T., Silva M., Gospodarowicz D., RA Fiddes J.C., Abraham J.A.; RT "The human gene for vascular endothelial growth factor. Multiple RT protein forms are encoded through alternative exon splicing."; RL J. Biol. Chem. 266:11947-11954(1991). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM VEGF206). RX PubMed=1791831; DOI=10.1210/mend-5-12-1806; RA Houck K.A., Ferrara N., Winer J., Cachianes G., Li B., Leung D.W.; RT "The vascular endothelial growth factor family: identification of a RT fourth molecular species and characterization of alternative splicing RT of RNA."; RL Mol. Endocrinol. 5:1806-1814(1991). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF165). RX PubMed=1567395; DOI=10.1016/S0006-291X(05)80313-4; RA Weindel K., Marme D., Weich H.A.; RT "AIDS-associated Kaposi's sarcoma cells in culture express vascular RT endothelial growth factor."; RL Biochem. Biophys. Res. Commun. 183:1167-1174(1992). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF145). RX PubMed=9054410; DOI=10.1074/jbc.272.11.7151; RA Poltorak Z., Cohen T., Sivan R., Kandelis Y., Spira G., Vlodavsky I., RA Keshet E., Neufeld G.; RT "VEGF145, a secreted vascular endothelial growth factor isoform that RT binds to extracellular matrix."; RL J. Biol. Chem. 272:7151-7158(1997). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF183). RC TISSUE=Kidney; RX PubMed=9878851; DOI=10.1016/S0167-4781(98)00240-1; RA Lei J., Jiang A., Pei D.; RT "Identification and characterization of a new splicing variant of RT vascular endothelial growth factor: VEGF183."; RL Biochim. Biophys. Acta 1443:400-406(1998). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM L-VEGF165). RC TISSUE=Mammary gland; RX PubMed=9450968; DOI=10.1091/mbc.9.2.469; RA Claffey K.P., Shih S.-C., Mullen A., Dziennis S., Cusick J.L., RA Abrams K.R., Lee S.W., Detmar M.; RT "Identification of a human VPF/VEGF 3' untranslated region mediating RT hypoxia-induced mRNA stability."; RL Mol. Biol. Cell 9:469-481(1998). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF148). RC TISSUE=Renal glomerulus; RX PubMed=10464055; DOI=10.1042/CS19990016; RA Whittle C.J., Gillespie K.M., Harrison R., Mathieson P.W., RA Harper S.J.; RT "Heterogeneous vascular endothelial growth factor (VEGF) isoform mRNA RT and receptor mRNA expression in human glomeruli, and the RT identification of VEGF148 mRNA, a novel truncated splice variant."; RL Clin. Sci. 97:303-312(1999). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF165B). RC TISSUE=Kidney; RX PubMed=12124351; RA Bates D.O., Cui T.-G., Doughty J.M., Winkler M., Sugiono M., RA Shields J.D., Peat D., Gillatt D., Harper S.J.; RT "VEGF165b, an inhibitory splice variant of vascular endothelial growth RT factor, is down-regulated in renal cell carcinoma."; RL Cancer Res. 62:4123-4131(2002). RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF165). RC TISSUE=Hemangioendothelioma; RA Murata H., Fukushima J., Hattori S., Okuda K., Yanagi H.; RT "Human cDNA for the vascular endothelial growth factor isoform RT VEGF165."; RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF121). RA Sato J.D., Whitney R.G.; RT "Human cDNA for vascular endothelial growth factor isoform VEGF121."; RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases. RN [13] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF165). RA Liu J., Peng X., Yuan J., Qiang B.; RT "Cloning of vascular endothelial growth factor (VEGF) cDNA."; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. RN [14] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF165). RC TISSUE=Heart; RA Shan Z.X., Yu X.Y., Lin Q.X., Fu Y.H., Zheng M., Tan H.H., Lin S.G.; RT "Cloning and identification of vascular endothelial growth factor RT isoform VEGF165."; RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases. RN [15] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF165). RA Koul S., Johnson T., Meacham R.B., Koul H.K.; RT "Cloning and characterization of VEGF from LNCaP cells, a line of RT prostate cancer cells."; RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases. RN [16] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VEGF111). RA Mineur P.J., Colige A.C., Lambert C.A.; RT "VEGF111, a new VEGF-A variant lacking exons 5, 6 and 7."; RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases. RN [17] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM VEGF165). RX PubMed=19054851; DOI=10.1038/nmeth.1273; RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B., RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., RA Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., RA Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., RA Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., RA Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., RA Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., RA Isogai T., Imai J., Watanabe S., Nomura N.; RT "Human protein factory for converting the transcriptome into an in RT vitro-expressed proteome."; RL Nat. Methods 5:1011-1017(2008). RN [18] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [19] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [20] RP PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM L-VEGF121). RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [21] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 23-232. RG SeattleSNPs variation discovery resource; RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases. RN [22] RP PROTEIN SEQUENCE OF 27-41. RX PubMed=7678805; DOI=10.1111/j.1432-1033.1993.tb19865.x; RA Fiebich B.L., Jaeger B., Schoellmann C., Weindel K., Wilting J., RA Kochs G., Marme D., Hug H., Weich H.A.; RT "Synthesis and assembly of functionally active human vascular RT endothelial growth factor homodimers in insect cells."; RL Eur. J. Biochem. 211:19-26(1993). RN [23] RP PROTEIN SEQUENCE OF 27-41. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally RT verified cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [24] RP PRELIMINARY PROTEIN SEQUENCE OF 27-36; 43-50 AND 59-81. RX PubMed=2584205; RA Connolly D.T., Olander J.V., Heuvelman D., Nelson R., Monsell R., RA Siegel N., Haymore B.L., Leimgruber R., Feder J.; RT "Human vascular permeability factor. Isolation from U937 cells."; RL J. Biol. Chem. 264:20017-20024(1989). RN [25] RP NUCLEOTIDE SEQUENCE [MRNA] OF 114-209 (ISOFORM VEGF183). RC TISSUE=Retina; RX PubMed=10067980; RA Jingjing L., Xue Y., Agarwal N., Roque R.S.; RT "Human Muller cells express VEGF183, a novel spliced variant of RT vascular endothelial growth factor."; RL Invest. Ophthalmol. Vis. Sci. 40:752-759(1999). RN [26] RP ALTERNATIVE SPLICING (ISOFORMS L-VEGF121 AND L-VEGF165), PROCESSING, RP AND SUBCELLULAR LOCATION. RX PubMed=11563986; DOI=10.1042/0264-6021:3590219; RA Tee M.K., Jaffe R.B.; RT "A precursor form of vascular endothelial growth factor arises by RT initiation from an upstream in-frame CUG codon."; RL Biochem. J. 359:219-226(2001). RN [27] RP FUNCTION. RX PubMed=11427521; RA Murphy J.F., Fitzgerald D.J.; RT "Vascular endothelial growth factor induces cyclooxygenase-dependent RT proliferation of endothelial cells via the VEGF-2 receptor."; RL FASEB J. 15:1667-1669(2001). RN [28] RP ALTERNATIVE SPLICING (ISOFORM L-VEGF189), PROCESSING, AND SUBCELLULAR RP LOCATION. RX PubMed=11731620; DOI=10.1210/me.15.12.2197; RA Huez I., Bornes S., Bresson D., Creancier L., Prats H.; RT "New vascular endothelial growth factor isoform generated by internal RT ribosome entry site-driven CUG translation initiation."; RL Mol. Endocrinol. 15:2197-2210(2001). RN [29] RP INVOLVEMENT IN MICROVASCULAR COMPLICATIONS OF DIABETES. RX PubMed=11978667; DOI=10.2337/diabetes.51.5.1635; RA Awata T., Inoue K., Kurihara S., Ohkubo T., Watanabe M., Inukai K., RA Inoue I., Katayama S.; RT "A common polymorphism in the 5'-untranslated region of the VEGF gene RT is associated with diabetic retinopathy in type 2 diabetes."; RL Diabetes 51:1635-1639(2002). RN [30] RP FUNCTION (ISOFORM VEGF165B). RX PubMed=15520188; DOI=10.1158/0008-5472.CAN-04-0934; RA Woolard J., Wang W.-Y., Bevan H.S., Qiu Y., Morbidelli L., RA Pritchard-Jones R.O., Cui T.-G., Sugiono M., Waine E., Perrin R., RA Foster R., Digby-Bell J., Shields J.D., Whittles C.E., Mushens R.E., RA Gillatt D.A., Ziche M., Harper S.J., Bates D.O.; RT "VEGF165b, an inhibitory vascular endothelial growth factor splice RT variant: mechanism of action, in vivo effect on angiogenesis and RT endogenous protein expression."; RL Cancer Res. 64:7822-7835(2004). RN [31] RP ALTERNATIVE SPLICING (ISOFORMS L-VEGF121; L-VEGF165 AND L-VEGF189). RX PubMed=14764596; DOI=10.1074/jbc.M308410200; RA Bornes S., Boulard M., Hieblot C., Zanibellato C., Iacovoni J.S., RA Prats H., Touriol C.; RT "Control of the vascular endothelial growth factor internal ribosome RT entry site (IRES) activity and translation initiation by alternatively RT spliced coding sequences."; RL J. Biol. Chem. 279:18717-18726(2004). RN [32] RP ALTERNATIVE SPLICING (ISOFORMS L-VEGF121 AND L-VEGF165), PROCESSING, RP AND SUBCELLULAR LOCATION. RX PubMed=15896327; DOI=10.1016/j.bbrc.2005.04.123; RA Rosenbaum-Dekel Y., Fuchs A., Yakirevich E., Azriel A., Mazareb S., RA Resnick M.B., Levi B.Z.; RT "Nuclear localization of long-VEGF is associated with hypoxia and RT tumor angiogenesis."; RL Biochem. Biophys. Res. Commun. 332:271-278(2005). RN [33] RP FUNCTION IN CELL MIGRATION. RX PubMed=16489009; DOI=10.1158/0008-5472.CAN-05-2217; RA Dixelius J., Olsson A.K., Thulin A., Lee C., Johansson I., RA Claesson-Welsh L.; RT "Minimal active domain and mechanism of action of the angiogenesis RT inhibitor histidine-rich glycoprotein."; RL Cancer Res. 66:2089-2097(2006). RN [34] RP TISSUE SPECIFICITY, AND INDUCTION. RX PubMed=22009797; DOI=10.1530/ERC-11-0211; RA Shan B., Gerez J., Haedo M., Fuertes M., Theodoropoulou M., RA Buchfelder M., Losa M., Stalla G.K., Arzt E., Renner U.; RT "RSUME is implicated in HIF-1-induced VEGF-A production in pituitary RT tumour cells."; RL Endocr. Relat. Cancer 19:13-27(2012). RN [35] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 34-135. RX PubMed=9207067; DOI=10.1073/pnas.94.14.7192; RA Muller Y.A., Li B., Christinger H.W., Wells J.A., Cunningham B.C., RA de Vos A.M.; RT "Vascular endothelial growth factor: crystal structure and functional RT mapping of the kinase domain receptor binding site."; RL Proc. Natl. Acad. Sci. U.S.A. 94:7192-7197(1997). RN [36] RP STRUCTURE BY NMR OF 34-135. RX PubMed=9336848; DOI=10.1002/pro.5560061020; RA Fairbrother W.J., Champe M.A., Christinger H.W., Keyt B.A., RA Starovasnik M.A.; RT "1H, 13C, and 15N backbone assignment and secondary structure of the RT receptor-binding domain of vascular endothelial growth factor."; RL Protein Sci. 6:2250-2260(1997). RN [37] RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 34-135. RX PubMed=9351807; DOI=10.1016/S0969-2126(97)00284-0; RA Muller Y.A., Christinger H.W., Keyt B.A., de Vos A.M.; RT "The crystal structure of vascular endothelial growth factor (VEGF) RT refined to 1.93-A resolution: multiple copy flexibility and receptor RT binding."; RL Structure 5:1325-1338(1997). RN [38] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 39-134. RX PubMed=9922142; DOI=10.1021/bi9819327; RA Wiesmann C., Christinger H.W., Cochran A.G., Cunningham B.C., RA Fairbrother W.J., Keenan C.J., Meng G., de Vos A.M.; RT "Crystal structure of the complex between VEGF and a receptor-blocking RT peptide."; RL Biochemistry 37:17765-17772(1998). RN [39] RP STRUCTURE BY NMR OF 137-215. RX PubMed=9634701; DOI=10.1016/S0969-2126(98)00065-3; RA Fairbrother W.J., Champe M.A., Christinger H.W., Keyt B.A., RA Starovasnik M.A.; RT "Solution structure of the heparin-binding domain of vascular RT endothelial growth factor."; RL Structure 6:637-648(1998). CC -!- FUNCTION: Growth factor active in angiogenesis, vasculogenesis and CC endothelial cell growth. Induces endothelial cell proliferation, CC promotes cell migration, inhibits apoptosis and induces CC permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and CC KDR/VEGFR2 receptors, heparan sulfate and heparin. CC NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform CC VEGF165B binds to KDR but does not activate downstream signaling CC pathways, does not activate angiogenesis and inhibits tumor CC growth. {ECO:0000269|PubMed:11427521, CC ECO:0000269|PubMed:16489009}. CC -!- SUBUNIT: Homodimer; disulfide-linked. Also found as heterodimer CC with PGF (By similarity). {ECO:0000250}. CC -!- INTERACTION: CC Self; NbExp=10; IntAct=EBI-1026643, EBI-1026643; CC P17948:FLT1; NbExp=4; IntAct=EBI-1026643, EBI-1026718; CC P35968:KDR; NbExp=6; IntAct=EBI-1026691, EBI-1005487; CC O14786:NRP1; NbExp=4; IntAct=EBI-1026643, EBI-1187100; CC O14786-2:NRP1; NbExp=4; IntAct=EBI-1026691, EBI-6285281; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11563986, CC ECO:0000269|PubMed:11731620, ECO:0000269|PubMed:15896327}. CC Note=VEGF121 is acidic and freely secreted. VEGF165 is more basic, CC has heparin-binding properties and, although a signicant CC proportion remains cell-associated, most is freely secreted. CC VEGF189 is very basic, it is cell-associated after secretion and CC is bound avidly by heparin and the extracellular matrix, although CC it may be released as a soluble form by heparin, heparinase or CC plasmin. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing, Alternative initiation; Named isoforms=17; CC Comment=Additional isoforms seem to exist.; CC Name=VEGF206; CC IsoId=P15692-1; Sequence=Displayed; CC Name=VEGF189; CC IsoId=P15692-2; Sequence=VSP_004622; CC Name=VEGF183; CC IsoId=P15692-3; Sequence=VSP_004621; CC Name=VEGF165; Synonyms=VEGF; CC IsoId=P15692-4; Sequence=VSP_004618, VSP_004619; CC Name=VEGF148; CC IsoId=P15692-5; Sequence=VSP_004618, VSP_004619, VSP_004624, CC VSP_004625; CC Name=VEGF145; CC IsoId=P15692-6; Sequence=VSP_004623; CC Name=VEGF165B; CC IsoId=P15692-8; Sequence=VSP_004618, VSP_004619, VSP_014783; CC Name=VEGF121; CC IsoId=P15692-9; Sequence=VSP_004620; CC Note=No experimental confirmation available.; CC Name=VEGF111; CC IsoId=P15692-10; Sequence=VSP_026781; CC Note=No experimental confirmation available.; CC Name=L-VEGF165; CC IsoId=P15692-11; Sequence=VSP_038745, VSP_004618, VSP_004619; CC Note=Produced by alternative promoter usage and alternative CC initiation. Starts at an alternative upstream CUG codon. CC Post-translationally processed to produce the secreted VEGF CC peptide and a N-terminal peptide N-VEGF. The unprocessed protein CC and the N-VEGF peptide may localize to the nucleus CC (PubMed:15896327), the endoplasmic reticulum and the Golgi CC (PubMed:11731620) or the extracellular matrix (PubMed:11563986). CC {ECO:0000305|PubMed:11563986, ECO:0000305|PubMed:11731620, CC ECO:0000305|PubMed:15896327}; CC Name=L-VEGF121; CC IsoId=P15692-12; Sequence=VSP_038745, VSP_004620; CC Note=Produced by alternative promoter usage and alternative CC initiation. Starts at an alternative upstream CUG codon. CC Post-translationally processed to produce the secreted VEGF CC peptide and a N-terminal peptide N-VEGF. The unprocessed protein CC and the N-VEGF peptide may localize to the nucleus CC (PubMed:15896327), the endoplasmic reticulum and the Golgi CC (PubMed:11731620) or the extracellular matrix (PubMed:11563986). CC {ECO:0000305|PubMed:11563986, ECO:0000305|PubMed:11731620, CC ECO:0000305|PubMed:15896327}; CC Name=L-VEGF189; CC IsoId=P15692-13; Sequence=VSP_038745, VSP_004622; CC Note=Produced by alternative promoter usage and alternative CC initiation. Starts at an alternative upstream CUG codon. CC Post-translationally processed to produce the secreted VEGF CC peptide and a N-terminal peptide N-VEGF. The unprocessed protein CC and the N-VEGF peptide may localize to the nucleus CC (PubMed:15896327), the endoplasmic reticulum and the Golgi CC (PubMed:11731620) or the extracellular matrix (PubMed:11563986). CC {ECO:0000305|PubMed:11563986, ECO:0000305|PubMed:11731620, CC ECO:0000305|PubMed:15896327}; CC Name=L-VEGF206; CC IsoId=P15692-14; Sequence=VSP_038745; CC Note=Gene prediction based on EST data. Produced by alternative CC promoter usage and alternative initiation. Starts at an CC alternative upstream CUG codon.; CC Name=15; CC IsoId=P15692-15; Sequence=VSP_038745, VSP_054111, VSP_014783; CC Note=Starts at an alternative upstream CUG codon.; CC Name=16; CC IsoId=P15692-16; Sequence=VSP_038745, VSP_004621; CC Note=Starts at an alternative upstream CUG codon.; CC Name=17; CC IsoId=P15692-17; Sequence=VSP_038745, VSP_054111, VSP_004624, CC VSP_004625; CC Note=Starts at an alternative upstream CUG codon.; CC Name=18; CC IsoId=P15692-18; Sequence=VSP_038745, VSP_026781; CC Note=Starts at an alternative upstream CUG codon.; CC -!- TISSUE SPECIFICITY: Isoform VEGF189, isoform VEGF165 and isoform CC VEGF121 are widely expressed. Isoform VEGF206 and isoform VEGF145 CC are not widely expressed. A higher level expression seen in CC pituitary tumors as compared to the pituitary gland. CC {ECO:0000269|PubMed:22009797}. CC -!- INDUCTION: By hypoxia. Regulated by growth factors, cytokines, CC gonadotropins, nitric oxide, hypoglycemia and oncogenic mutations. CC {ECO:0000269|PubMed:22009797}. CC -!- DISEASE: Microvascular complications of diabetes 1 (MVCD1) CC [MIM:603933]: Pathological conditions that develop in numerous CC tissues and organs as a consequence of diabetes mellitus. They CC include diabetic retinopathy, diabetic nephropathy leading to end- CC stage renal disease, and diabetic neuropathy. Diabetic retinopathy CC remains the major cause of new-onset blindness among diabetic CC adults. It is characterized by vascular permeability and increased CC tissue ischemia and angiogenesis. Note=Disease susceptibility is CC associated with variations affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the PDGF/VEGF growth factor family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC63102.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAC63143.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305}; CC Sequence=CAC19512.2; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305}; CC Sequence=CAC19516.2; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=R&D Systems' cytokine mini-reviews: VEGF; CC URL="http://www.rndsystems.com/molecule_detail.aspx?m=2247"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=VEGF entry; CC URL="https://en.wikipedia.org/wiki/Vascular_endothelial_growth_factor"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/vegf/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M32977; AAA35789.1; -; mRNA. DR EMBL; M27281; AAA36807.1; -; mRNA. DR EMBL; M63978; AAA36804.1; -; Genomic_DNA. DR EMBL; M63971; AAA36804.1; JOINED; Genomic_DNA. DR EMBL; M63972; AAA36804.1; JOINED; Genomic_DNA. DR EMBL; M63973; AAA36804.1; JOINED; Genomic_DNA. DR EMBL; M63974; AAA36804.1; JOINED; Genomic_DNA. DR EMBL; M63975; AAA36804.1; JOINED; Genomic_DNA. DR EMBL; M63976; AAA36804.1; JOINED; Genomic_DNA. DR EMBL; M63977; AAA36804.1; JOINED; Genomic_DNA. DR EMBL; S85192; AAC63102.1; ALT_INIT; mRNA. DR EMBL; AH006909; AAC63101.1; -; Genomic_DNA. DR EMBL; X62568; CAA44447.1; -; mRNA. DR EMBL; AJ010438; CAA09179.1; -; mRNA. DR EMBL; AF022375; AAC63143.1; ALT_SEQ; mRNA. DR EMBL; AF091352; AAD55345.1; -; mRNA. DR EMBL; AF430806; AAL27435.1; -; mRNA. DR EMBL; AB021221; BAA78418.1; -; mRNA. DR EMBL; AF214570; AAF19659.1; -; mRNA. DR EMBL; AY047581; AAK95847.1; -; mRNA. DR EMBL; AF486837; AAM03108.1; -; mRNA. DR EMBL; AY766116; AAV34601.1; -; mRNA. DR EMBL; DQ229900; ABB58912.1; -; mRNA. DR EMBL; AB451322; BAG70136.1; -; mRNA. DR EMBL; AB451451; BAG70265.1; -; mRNA. DR EMBL; AL136131; CAC19512.2; ALT_SEQ; Genomic_DNA. DR EMBL; AL136131; CAC19513.2; -; Genomic_DNA. DR EMBL; AL136131; CAC19515.2; -; Genomic_DNA. DR EMBL; AL136131; CAC19516.2; ALT_SEQ; Genomic_DNA. DR EMBL; CH471081; EAX04229.1; -; Genomic_DNA. DR EMBL; BC065522; AAH65522.2; -; mRNA. DR EMBL; AF437895; AAL27630.1; -; Genomic_DNA. DR EMBL; AF062645; AAC16730.1; -; mRNA. DR CCDS; CCDS34457.1; -. [P15692-14] DR CCDS; CCDS34458.1; -. [P15692-11] DR CCDS; CCDS47432.1; -. [P15692-15] DR CCDS; CCDS47433.1; -. [P15692-16] DR CCDS; CCDS47434.1; -. [P15692-12] DR CCDS; CCDS47435.1; -. [P15692-17] DR CCDS; CCDS4907.2; -. [P15692-13] DR CCDS; CCDS55007.1; -. [P15692-18] DR CCDS; CCDS55008.1; -. [P15692-3] DR CCDS; CCDS55009.1; -. [P15692-2] DR CCDS; CCDS55010.1; -. [P15692-1] DR CCDS; CCDS55011.1; -. [P15692-5] DR CCDS; CCDS55012.1; -. [P15692-4] DR CCDS; CCDS55013.1; -. [P15692-8] DR CCDS; CCDS55014.1; -. [P15692-9] DR CCDS; CCDS55015.1; -. [P15692-10] DR PIR; A41551; A41551. DR RefSeq; NP_001020537.2; NM_001025366.2. [P15692-14] DR RefSeq; NP_001020538.2; NM_001025367.2. [P15692-16] DR RefSeq; NP_001020539.2; NM_001025368.2. [P15692-11] DR RefSeq; NP_001020540.2; NM_001025369.2. [P15692-17] DR RefSeq; NP_001020541.2; NM_001025370.2. [P15692-12] DR RefSeq; NP_001028928.1; NM_001033756.2. [P15692-15] DR RefSeq; NP_001165093.1; NM_001171622.1. [P15692-18] DR RefSeq; NP_001165094.1; NM_001171623.1. [P15692-1] DR RefSeq; NP_001165095.1; NM_001171624.1. [P15692-2] DR RefSeq; NP_001165096.1; NM_001171625.1. [P15692-3] DR RefSeq; NP_001165097.1; NM_001171626.1. [P15692-4] DR RefSeq; NP_001165098.1; NM_001171627.1. [P15692-5] DR RefSeq; NP_001165099.1; NM_001171628.1. [P15692-9] DR RefSeq; NP_001165100.1; NM_001171629.1. [P15692-8] DR RefSeq; NP_001165101.1; NM_001171630.1. [P15692-10] DR RefSeq; NP_001191313.1; NM_001204384.1. [P15692-6] DR RefSeq; NP_001191314.1; NM_001204385.1. DR RefSeq; NP_001273973.1; NM_001287044.1. DR RefSeq; NP_003367.4; NM_003376.5. [P15692-13] DR UniGene; Hs.73793; -. DR PDB; 1BJ1; X-ray; 2.40 A; V/W=34-135. DR PDB; 1CZ8; X-ray; 2.40 A; V/W=40-133. DR PDB; 1FLT; X-ray; 1.70 A; V/W=38-135. DR PDB; 1KAT; NMR; -; V/W=37-135. DR PDB; 1KMX; NMR; -; A=183-232. DR PDB; 1MJV; X-ray; 2.10 A; A/B=40-134. DR PDB; 1MKG; X-ray; 2.50 A; A/B/C/D=40-134. DR PDB; 1MKK; X-ray; 1.32 A; A/B=40-134. DR PDB; 1QTY; X-ray; 2.70 A; R/S/V/W=34-135. DR PDB; 1TZH; X-ray; 2.60 A; V/W=34-135. DR PDB; 1TZI; X-ray; 2.80 A; V=34-135. DR PDB; 1VGH; NMR; -; A=180-232. DR PDB; 1VPF; X-ray; 2.50 A; A/B/C/D=34-135. DR PDB; 1VPP; X-ray; 1.90 A; V/W=34-135. DR PDB; 2FJG; X-ray; 2.80 A; V/W=34-135. DR PDB; 2FJH; X-ray; 3.10 A; V/W=34-135. DR PDB; 2QR0; X-ray; 3.50 A; C/D/I/J/O/P/U/V=39-135. DR PDB; 2VGH; NMR; -; A=182-232. DR PDB; 2VPF; X-ray; 1.93 A; A/B/C/D/E/F/G/H=34-135. DR PDB; 3BDY; X-ray; 2.60 A; V=34-135. DR PDB; 3P9W; X-ray; 2.41 A; A/C/E/G=35-138. DR PDB; 3QTK; X-ray; 1.85 A; A/B/C/D/E/F=34-135. DR PDB; 3S1B; X-ray; 2.90 A; V=38-133. DR PDB; 3S1K; X-ray; 2.55 A; V/W=34-135. DR PDB; 3V2A; X-ray; 3.20 A; A=27-140. DR PDB; 4DEQ; X-ray; 2.65 A; A/B=183-232. DR PDB; 4GLN; X-ray; 1.60 A; E/F=34-135. DR PDB; 4GLS; X-ray; 1.60 A; E/F=34-135. DR PDB; 4KZN; X-ray; 1.71 A; A=39-135. DR PDB; 4QAF; X-ray; 1.80 A; C/D=34-135. DR PDB; 4WPB; X-ray; 3.11 A; A/B=34-135. DR PDB; 4ZFF; X-ray; 2.75 A; C/D=37-135. DR PDBsum; 1BJ1; -. DR PDBsum; 1CZ8; -. DR PDBsum; 1FLT; -. DR PDBsum; 1KAT; -. DR PDBsum; 1KMX; -. DR PDBsum; 1MJV; -. DR PDBsum; 1MKG; -. DR PDBsum; 1MKK; -. DR PDBsum; 1QTY; -. DR PDBsum; 1TZH; -. DR PDBsum; 1TZI; -. DR PDBsum; 1VGH; -. DR PDBsum; 1VPF; -. DR PDBsum; 1VPP; -. DR PDBsum; 2FJG; -. DR PDBsum; 2FJH; -. DR PDBsum; 2QR0; -. DR PDBsum; 2VGH; -. DR PDBsum; 2VPF; -. DR PDBsum; 3BDY; -. DR PDBsum; 3P9W; -. DR PDBsum; 3QTK; -. DR PDBsum; 3S1B; -. DR PDBsum; 3S1K; -. DR PDBsum; 3V2A; -. DR PDBsum; 4DEQ; -. DR PDBsum; 4GLN; -. DR PDBsum; 4GLS; -. DR PDBsum; 4KZN; -. DR PDBsum; 4QAF; -. DR PDBsum; 4WPB; -. DR PDBsum; 4ZFF; -. DR ProteinModelPortal; P15692; -. DR SMR; P15692; 39-133, 183-232. DR BioGrid; 113265; 28. DR DIP; DIP-5740N; -. DR IntAct; P15692; 16. DR MINT; MINT-2834049; -. DR STRING; 9606.ENSP00000361125; -. DR BindingDB; P15692; -. DR ChEMBL; CHEMBL1783; -. DR DrugBank; DB08885; Aflibercept. DR DrugBank; DB00112; Bevacizumab. DR DrugBank; DB01136; Carvedilol. DR DrugBank; DB06779; Dalteparin. DR DrugBank; DB01120; Gliclazide. DR DrugBank; DB01017; Minocycline. DR DrugBank; DB01270; Ranibizumab. DR DrugBank; DB05294; Vandetanib. DR GuidetoPHARMACOLOGY; 2644; -. DR PhosphoSite; P15692; -. DR BioMuta; VEGFA; -. DR DMDM; 17380528; -. DR PaxDb; P15692; -. DR PRIDE; P15692; -. DR DNASU; 7422; -. DR Ensembl; ENST00000372077; ENSP00000361148; ENSG00000112715. [P15692-9] DR Ensembl; ENST00000457104; ENSP00000409911; ENSG00000112715. [P15692-10] DR Ensembl; ENST00000518689; ENSP00000430829; ENSG00000112715. [P15692-3] DR Ensembl; ENST00000518824; ENSP00000430002; ENSG00000112715. [P15692-8] DR Ensembl; ENST00000520948; ENSP00000428321; ENSG00000112715. [P15692-2] DR Ensembl; ENST00000523125; ENSP00000429008; ENSG00000112715. [P15692-5] DR Ensembl; ENST00000523873; ENSP00000430479; ENSG00000112715. [P15692-1] DR Ensembl; ENST00000523950; ENSP00000429643; ENSG00000112715. [P15692-4] DR GeneID; 7422; -. DR KEGG; hsa:7422; -. DR UCSC; uc003owd.3; human. [P15692-5] DR UCSC; uc003owe.3; human. [P15692-4] DR UCSC; uc003owf.3; human. [P15692-13] DR UCSC; uc003owg.3; human. [P15692-3] DR UCSC; uc003owh.3; human. [P15692-1] DR UCSC; uc003owi.3; human. [P15692-8] DR UCSC; uc003owj.3; human. [P15692-9] DR UCSC; uc010jyx.3; human. [P15692-10] DR CTD; 7422; -. DR GeneCards; VEGFA; -. DR HGNC; HGNC:12680; VEGFA. DR HPA; CAB005429; -. DR MIM; 192240; gene. DR MIM; 603933; phenotype. DR neXtProt; NX_P15692; -. DR PharmGKB; PA37302; -. DR eggNOG; ENOG410IGCM; Eukaryota. DR eggNOG; ENOG410ZWYU; LUCA. DR GeneTree; ENSGT00730000110791; -. DR HOVERGEN; HBG000105; -. DR InParanoid; P15692; -. DR KO; K05448; -. DR PhylomeDB; P15692; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-1234158; Regulation of gene expression by Hypoxia-inducible Factor. DR Reactome; R-HSA-194313; VEGF ligand-receptor interactions. DR Reactome; R-HSA-195399; VEGF binds to VEGFR leading to receptor dimerization. DR Reactome; R-HSA-3928663; EPHA-mediated growth cone collapse. DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway. DR Reactome; R-HSA-5218921; VEGFR2 mediated cell proliferation. DR ChiTaRS; VEGFA; human. DR EvolutionaryTrace; P15692; -. DR GeneWiki; Vascular_endothelial_growth_factor_A; -. DR GenomeRNAi; 7422; -. DR NextBio; 29060; -. DR PRO; PR:P15692; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; P15692; -. DR ExpressionAtlas; P15692; baseline and differential. DR Genevisible; P15692; HS. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IEA:InterPro. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0005578; C:proteinaceous extracellular matrix; NAS:UniProtKB. DR GO; GO:0030141; C:secretory granule; IDA:UniProtKB. DR GO; GO:0042056; F:chemoattractant activity; IDA:UniProtKB. DR GO; GO:0005125; F:cytokine activity; IDA:BHF-UCL. DR GO; GO:0050840; F:extracellular matrix binding; IC:BHF-UCL. DR GO; GO:0001968; F:fibronectin binding; IDA:BHF-UCL. DR GO; GO:0008083; F:growth factor activity; IDA:BHF-UCL. DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0038191; F:neuropilin binding; IPI:BHF-UCL. DR GO; GO:0005161; F:platelet-derived growth factor receptor binding; IPI:BHF-UCL. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:MGI. DR GO; GO:0042803; F:protein homodimerization activity; ISS:BHF-UCL. DR GO; GO:0048018; F:receptor agonist activity; IPI:BHF-UCL. DR GO; GO:0043183; F:vascular endothelial growth factor receptor 1 binding; IPI:BHF-UCL. DR GO; GO:0043184; F:vascular endothelial growth factor receptor 2 binding; IPI:BHF-UCL. DR GO; GO:0005172; F:vascular endothelial growth factor receptor binding; IPI:UniProtKB. DR GO; GO:0032147; P:activation of protein kinase activity; IDA:BHF-UCL. DR GO; GO:0001525; P:angiogenesis; IDA:UniProtKB. DR GO; GO:0048844; P:artery morphogenesis; ISS:BHF-UCL. DR GO; GO:0002575; P:basophil chemotaxis; IDA:UniProtKB. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISS:BHF-UCL. DR GO; GO:0048593; P:camera-type eye morphogenesis; ISS:BHF-UCL. DR GO; GO:0048739; P:cardiac muscle fiber development; ISS:BHF-UCL. DR GO; GO:0060948; P:cardiac vascular smooth muscle cell development; ISS:BHF-UCL. DR GO; GO:0048469; P:cell maturation; ISS:BHF-UCL. DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; IDA:BHF-UCL. DR GO; GO:0071456; P:cellular response to hypoxia; IDA:MGI. DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IDA:BHF-UCL. DR GO; GO:0071679; P:commissural neuron axon guidance; ISS:BHF-UCL. DR GO; GO:0060982; P:coronary artery morphogenesis; ISS:BHF-UCL. DR GO; GO:0003169; P:coronary vein morphogenesis; ISS:BHF-UCL. DR GO; GO:0071542; P:dopaminergic neuron differentiation; ISS:BHF-UCL. DR GO; GO:0035767; P:endothelial cell chemotaxis; IDA:BHF-UCL. DR GO; GO:0030855; P:epithelial cell differentiation; ISS:BHF-UCL. DR GO; GO:0042462; P:eye photoreceptor cell development; ISS:BHF-UCL. DR GO; GO:0040007; P:growth; ISS:BHF-UCL. DR GO; GO:0003007; P:heart morphogenesis; ISS:BHF-UCL. DR GO; GO:0001701; P:in utero embryonic development; ISS:BHF-UCL. DR GO; GO:0050930; P:induction of positive chemotaxis; IDA:UniProtKB. DR GO; GO:0001822; P:kidney development; ISS:BHF-UCL. DR GO; GO:0007595; P:lactation; ISS:BHF-UCL. DR GO; GO:0030324; P:lung development; ISS:BHF-UCL. DR GO; GO:0036303; P:lymph vessel morphogenesis; ISS:BHF-UCL. DR GO; GO:0030225; P:macrophage differentiation; IDA:DFLAT. DR GO; GO:0060749; P:mammary gland alveolus development; ISS:BHF-UCL. DR GO; GO:0007498; P:mesoderm development; ISS:BHF-UCL. DR GO; GO:0030224; P:monocyte differentiation; IDA:DFLAT. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL. DR GO; GO:0007399; P:nervous system development; TAS:UniProtKB. DR GO; GO:0003151; P:outflow tract morphogenesis; ISS:BHF-UCL. DR GO; GO:0001541; P:ovarian follicle development; ISS:BHF-UCL. DR GO; GO:0001569; P:patterning of blood vessels; ISS:BHF-UCL. DR GO; GO:0030168; P:platelet activation; TAS:Reactome. DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome. DR GO; GO:0050918; P:positive chemotaxis; IDA:BHF-UCL. DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:UniProtKB. DR GO; GO:0048842; P:positive regulation of axon extension involved in axon guidance; ISS:BHF-UCL. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IDA:BHF-UCL. DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; ISS:BHF-UCL. DR GO; GO:0045785; P:positive regulation of cell adhesion; IDA:UniProtKB. DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW. DR GO; GO:0030335; P:positive regulation of cell migration; IDA:BHF-UCL. DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; IDA:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell proliferation; IDA:BHF-UCL. DR GO; GO:0038091; P:positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0051272; P:positive regulation of cellular component movement; IDA:BHF-UCL. DR GO; GO:0032793; P:positive regulation of CREB transcription factor activity; IDA:BHF-UCL. DR GO; GO:0038033; P:positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IDA:UniProtKB. DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:UniProtKB. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISS:BHF-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:BHF-UCL. DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB. DR GO; GO:1901727; P:positive regulation of histone deacetylase activity; IDA:BHF-UCL. DR GO; GO:0002687; P:positive regulation of leukocyte migration; TAS:BHF-UCL. DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:BHF-UCL. DR GO; GO:0060754; P:positive regulation of mast cell chemotaxis; IDA:UniProtKB. DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; ISS:BHF-UCL. DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; ISS:BHF-UCL. DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; IDA:UniProtKB. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL. DR GO; GO:1900086; P:positive regulation of peptidyl-tyrosine autophosphorylation; IDA:BHF-UCL. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL. DR GO; GO:0050927; P:positive regulation of positive chemotaxis; IDA:BHF-UCL. DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; IDA:BHF-UCL. DR GO; GO:0031334; P:positive regulation of protein complex assembly; IDA:UniProtKB. DR GO; GO:0090037; P:positive regulation of protein kinase C signaling; IDA:BHF-UCL. DR GO; GO:1903572; P:positive regulation of protein kinase D signaling; IDA:BHF-UCL. DR GO; GO:1902966; P:positive regulation of protein localization to early endosome; IDA:BHF-UCL. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB. DR GO; GO:0002092; P:positive regulation of receptor internalization; IDA:BHF-UCL. DR GO; GO:1902336; P:positive regulation of retinal ganglion cell axon guidance; ISS:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL. DR GO; GO:0061419; P:positive regulation of transcription from RNA polymerase II promoter in response to hypoxia; IMP:BHF-UCL. DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0043117; P:positive regulation of vascular permeability; IDA:UniProtKB. DR GO; GO:0031077; P:post-embryonic camera-type eye development; ISS:BHF-UCL. DR GO; GO:0060319; P:primitive erythrocyte differentiation; ISS:BHF-UCL. DR GO; GO:0008360; P:regulation of cell shape; IDA:BHF-UCL. DR GO; GO:0030823; P:regulation of cGMP metabolic process; IDA:MGI. DR GO; GO:0090259; P:regulation of retinal ganglion cell axon guidance; ISS:BHF-UCL. DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL. DR GO; GO:0061418; P:regulation of transcription from RNA polymerase II promoter in response to hypoxia; TAS:Reactome. DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB. DR GO; GO:0043129; P:surfactant homeostasis; ISS:BHF-UCL. DR GO; GO:0035148; P:tube formation; IDA:UniProtKB. DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; IDA:BHF-UCL. DR GO; GO:0001570; P:vasculogenesis; TAS:UniProtKB. DR GO; GO:0038190; P:VEGF-activated neuropilin signaling pathway; ISS:BHF-UCL. DR Gene3D; 2.10.160.10; -; 1. DR Gene3D; 2.10.90.10; -; 1. DR InterPro; IPR029034; Cystine-knot_cytokine. DR InterPro; IPR023581; PD_growth_factor_CS. DR InterPro; IPR000072; PDGF/VEGF_dom. DR InterPro; IPR027928; VEGF_C. DR Pfam; PF00341; PDGF; 1. DR Pfam; PF14554; VEGF_C; 1. DR SMART; SM00141; PDGF; 1. DR SUPFAM; SSF57501; SSF57501; 1. DR SUPFAM; SSF57593; SSF57593; 1. DR PROSITE; PS00249; PDGF_1; 1. DR PROSITE; PS50278; PDGF_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative initiation; Alternative promoter usage; KW Alternative splicing; Angiogenesis; Complete proteome; KW Developmental protein; Differentiation; Direct protein sequencing; KW Disulfide bond; Glycoprotein; Growth factor; Heparin-binding; Mitogen; KW Reference proteome; Secreted; Signal. FT SIGNAL 1 26 {ECO:0000269|PubMed:15340161, FT ECO:0000269|PubMed:7678805}. FT CHAIN 27 232 Vascular endothelial growth factor A. FT /FTId=PRO_0000023386. FT CARBOHYD 101 101 N-linked (GlcNAc...). FT DISULFID 52 94 FT DISULFID 77 77 Interchain. FT DISULFID 83 128 FT DISULFID 86 86 Interchain. FT DISULFID 87 130 FT VAR_SEQ 1 1 M -> MTDRQTDTAPSPSYHLLPGRRRTVDAAASRGQGPEP FT APGGGVEGVGARGVALKLFVQLLGCSRFGGAVVRAGEAEPS FT GAARSASSGREEPQPEEGEEEEEKEEERGPQWRLGARKPGS FT WTGEAAVCADSAPAARAPQALARASGRGGRVARRGAEESGP FT PHSPSRRGSASRAGPGRASETM (in isoform L- FT VEGF165, isoform L-VEGF121, isoform L- FT VEGF189, isoform L-VEGF206, isoform 15, FT isoform 16, isoform 17 and isoform 18). FT {ECO:0000303|PubMed:9450968}. FT /FTId=VSP_038745. FT VAR_SEQ 132 226 Missing (in isoform VEGF111 and isoform FT 18). {ECO:0000303|Ref.16}. FT /FTId=VSP_026781. FT VAR_SEQ 141 182 KKSVRGKGKGQKRKRKKSRYKSWSVYVGARCCLMPWSLPGP FT H -> N (in isoform 15 and isoform 17). FT {ECO:0000305}. FT /FTId=VSP_054111. FT VAR_SEQ 141 141 K -> N (in isoform VEGF148, isoform FT VEGF165, isoform VEGF165B and isoform L- FT VEGF165). {ECO:0000303|PubMed:10464055, FT ECO:0000303|PubMed:12124351, FT ECO:0000303|PubMed:1567395, FT ECO:0000303|PubMed:19054851, FT ECO:0000303|PubMed:2479986, FT ECO:0000303|PubMed:9450968, FT ECO:0000303|Ref.11, ECO:0000303|Ref.13, FT ECO:0000303|Ref.14, ECO:0000303|Ref.15}. FT /FTId=VSP_004618. FT VAR_SEQ 142 226 Missing (in isoform VEGF121 and isoform FT L-VEGF121). {ECO:0000303|Ref.12}. FT /FTId=VSP_004620. FT VAR_SEQ 142 182 Missing (in isoform VEGF148, isoform FT VEGF165, isoform VEGF165B and isoform L- FT VEGF165). {ECO:0000303|PubMed:10464055, FT ECO:0000303|PubMed:12124351, FT ECO:0000303|PubMed:1567395, FT ECO:0000303|PubMed:19054851, FT ECO:0000303|PubMed:2479986, FT ECO:0000303|PubMed:9450968, FT ECO:0000303|Ref.11, ECO:0000303|Ref.13, FT ECO:0000303|Ref.14, ECO:0000303|Ref.15}. FT /FTId=VSP_004619. FT VAR_SEQ 160 182 Missing (in isoform VEGF183 and isoform FT 16). {ECO:0000303|PubMed:10067980, FT ECO:0000303|PubMed:9878851}. FT /FTId=VSP_004621. FT VAR_SEQ 166 226 Missing (in isoform VEGF145). FT {ECO:0000303|PubMed:9054410}. FT /FTId=VSP_004623. FT VAR_SEQ 166 182 Missing (in isoform VEGF189 and isoform FT L-VEGF189). {ECO:0000303|PubMed:2479986, FT ECO:0000303|PubMed:2479987}. FT /FTId=VSP_004622. FT VAR_SEQ 215 215 A -> M (in isoform VEGF148 and isoform FT 17). {ECO:0000303|PubMed:10464055}. FT /FTId=VSP_004624. FT VAR_SEQ 216 232 Missing (in isoform VEGF148 and isoform FT 17). {ECO:0000303|PubMed:10464055}. FT /FTId=VSP_004625. FT VAR_SEQ 227 232 CDKPRR -> SLTRKD (in isoform VEGF165B and FT isoform 15). FT {ECO:0000303|PubMed:12124351}. FT /FTId=VSP_014783. FT CONFLICT 87 87 C -> S (in Ref. 8; AAC63143). FT {ECO:0000305}. FT CONFLICT 210 210 D -> H (in Ref. 8; AAC63143). FT {ECO:0000305}. FT HELIX 43 50 {ECO:0000244|PDB:1MKK}. FT STRAND 51 60 {ECO:0000244|PDB:1MKK}. FT HELIX 61 64 {ECO:0000244|PDB:1MKK}. FT HELIX 66 68 {ECO:0000244|PDB:1MKK}. FT STRAND 71 84 {ECO:0000244|PDB:1MKK}. FT STRAND 93 109 {ECO:0000244|PDB:1MKK}. FT TURN 111 113 {ECO:0000244|PDB:4GLN}. FT STRAND 116 131 {ECO:0000244|PDB:1MKK}. FT STRAND 189 191 {ECO:0000244|PDB:1KMX}. FT HELIX 192 194 {ECO:0000244|PDB:4DEQ}. FT STRAND 195 197 {ECO:0000244|PDB:4DEQ}. FT TURN 199 201 {ECO:0000244|PDB:4DEQ}. FT STRAND 204 208 {ECO:0000244|PDB:4DEQ}. FT HELIX 210 215 {ECO:0000244|PDB:4DEQ}. FT STRAND 219 221 {ECO:0000244|PDB:4DEQ}. FT TURN 222 225 {ECO:0000244|PDB:4DEQ}. FT STRAND 226 228 {ECO:0000244|PDB:4DEQ}. SQ SEQUENCE 232 AA; 27042 MW; FB49F364446F4D01 CRC64; MNFLLSWVHW SLALLLYLHH AKWSQAAPMA EGGGQNHHEV VKFMDVYQRS YCHPIETLVD IFQEYPDEIE YIFKPSCVPL MRCGGCCNDE GLECVPTEES NITMQIMRIK PHQGQHIGEM SFLQHNKCEC RPKKDRARQE KKSVRGKGKG QKRKRKKSRY KSWSVYVGAR CCLMPWSLPG PHPCGPCSER RKHLFVQDPQ TCKCSCKNTD SRCKARQLEL NERTCRCDKP RR //