ID VGFR2_HUMAN Reviewed; 1356 AA. AC P35968; A2RRS0; B5A925; C5IFA0; O60723; Q14178; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 2. DT 24-JAN-2024, entry version 243. DE RecName: Full=Vascular endothelial growth factor receptor 2 {ECO:0000305}; DE Short=VEGFR-2; DE EC=2.7.10.1 {ECO:0000269|PubMed:10037737, ECO:0000269|PubMed:10102632}; DE AltName: Full=Fetal liver kinase 1; DE Short=FLK-1; DE AltName: Full=Kinase insert domain receptor; DE Short=KDR; DE AltName: Full=Protein-tyrosine kinase receptor flk-1; DE AltName: CD_antigen=CD309; DE Flags: Precursor; GN Name=KDR {ECO:0000312|HGNC:HGNC:6307}; Synonyms=FLK1, VEGFR2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), INTERACTION WITH VEGFC, AND RP SUBCELLULAR LOCATION. RX PubMed=18593464; DOI=10.1186/ar2447; RA Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., RA Phillips S., Feldmann M., Shepard H.M., Paleolog E.M.; RT "Novel splice variants derived from the receptor tyrosine kinase RT superfamily are potential therapeutics for rheumatoid arthritis."; RL Arthritis Res. Ther. 10:R73-R73(2008). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION IN INHIBITION OF RP LYMPHANGIOGENESIS, INTERACTION WITH VEGFC, AND TISSUE SPECIFICITY. RX PubMed=19668192; DOI=10.1038/nm.2018; RA Albuquerque R.J., Hayashi T., Cho W.G., Kleinman M.E., Dridi S., Takeda A., RA Baffi J.Z., Yamada K., Kaneko H., Green M.G., Chappell J., Wilting J., RA Weich H.A., Yamagami S., Amano S., Mizuki N., Alexander J.S., RA Peterson M.L., Brekken R.A., Hirashima M., Capoor S., Usui T., Ambati B.K., RA Ambati J.; RT "Alternatively spliced vascular endothelial growth factor receptor-2 is an RT essential endogenous inhibitor of lymphatic vessel growth."; RL Nat. Med. 15:1023-1030(2009). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Yin L.Y., Wu Y., Patterson C.; RT "Full length human KDR/flk-1 sequence."; RL Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Umbilical vein; RA Yu Y., Whitney R.G., Sato J.D.; RT "Coding region for human VEGF receptor KDR (VEGFR-2)."; RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT HIS-472. 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-1356 (ISOFORM 1), AND VARIANT GLU-848. RC TISSUE=Umbilical vein; RX PubMed=1656371; RA Terman B.I., Carrion M.E., Kovacs E., Rasmussen B.A., Eddy R.L., RA Shows T.B.; RT "Identification of a new endothelial cell growth factor receptor tyrosine RT kinase."; RL Oncogene 6:1677-1683(1991). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22. RX PubMed=7559454; DOI=10.1074/jbc.270.39.23111; RA Patterson C., Perrella M.A., Hsieh C.-M., Yoshizumi M., Lee M.-E., RA Harber E.; RT "Cloning and functional analysis of the promoter for KDR/flk-1, a receptor RT for vascular endothelial growth factor."; RL J. Biol. Chem. 270:23111-23118(1995). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH VEGFA. RX PubMed=1417831; DOI=10.1016/0006-291x(92)90483-2; RA Terman B.I., Dougher-Vermazen M., Carrion M.E., Dimitrov D., RA Armellino D.C., Gospodarowicz D., Boehlen P.; RT "Identification of the KDR tyrosine kinase as a receptor for vascular RT endothelial cell growth factor."; RL Biochem. Biophys. Res. Commun. 187:1579-1586(1992). RN [10] RP FUNCTION AS VEGFA RECEPTOR; IN REGULATION OF CELL SHAPE; ACTIN CYTOSKELETON RP REORGANIZATION; CELL MIGRATION AND CELL PROLIFERATION, AND RP AUTOPHOSPHORYLATION. RX PubMed=7929439; DOI=10.1016/s0021-9258(18)47116-5; RA Waltenberger J., Claesson-Welsh L., Siegbahn A., Shibuya M., Heldin C.H.; RT "Different signal transduction properties of KDR and Flt1, two receptors RT for vascular endothelial growth factor."; RL J. Biol. Chem. 269:26988-26995(1994). RN [11] RP FUNCTION IN VEGFA SIGNALING; PHOSPHORYLATION OF PLCG1; ACTIVATION OF MAP RP KINASES AND IN PROMOTING PROLIFERATION OF ENDOTHELIAL CELLS, INTERACTION RP WITH VEGFA AND PLCG1, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION, AND RP GLYCOSYLATION. RX PubMed=9160888; DOI=10.1038/sj.onc.1201047; RA Takahashi T., Shibuya M.; RT "The 230 kDa mature form of KDR/Flk-1 (VEGF receptor-2) activates the PLC- RT gamma pathway and partially induces mitotic signals in NIH3T3 RT fibroblasts."; RL Oncogene 14:2079-2089(1997). RN [12] RP FUNCTION IN INDUCTION OF NOS2 AND NOS3. RX PubMed=9837777; DOI=10.1006/bbrc.1998.9719; RA Kroll J., Waltenberger J.; RT "VEGF-A induces expression of eNOS and iNOS in endothelial cells via VEGF RT receptor-2 (KDR)."; RL Biochem. Biophys. Res. Commun. 252:743-746(1998). RN [13] RP FUNCTION IN ACTIVATION OF THE PHOSPHATIDYLINOSITOL 3-KINASE AND AKT1 RP SIGNALING PATHWAY. RX PubMed=9804796; DOI=10.1074/jbc.273.46.30336; RA Gerber H.P., McMurtrey A., Kowalski J., Yan M., Keyt B.A., Dixit V., RA Ferrara N.; RT "Vascular endothelial growth factor regulates endothelial cell survival RT through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. RT Requirement for Flk-1/KDR activation."; RL J. Biol. Chem. 273:30336-30343(1998). RN [14] RP FUNCTION IN NITRIC OXIDE RELEASE. RX PubMed=10600473; DOI=10.1006/bbrc.1999.1729; RA Kroll J., Waltenberger J.; RT "A novel function of VEGF receptor-2 (KDR): rapid release of nitric oxide RT in response to VEGF-A stimulation in endothelial cells."; RL Biochem. Biophys. Res. Commun. 265:636-639(1999). RN [15] RP CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANT GLU-848, PHOSPHORYLATION AT RP TYR-1054 AND TYR-1059, AND ACTIVITY REGULATION. RX PubMed=10037737; DOI=10.1074/jbc.274.10.6453; RA Kendall R.L., Rutledge R.Z., Mao X., Tebben A.J., Hungate R.W., RA Thomas K.A.; RT "Vascular endothelial growth factor receptor KDR tyrosine kinase activity RT is increased by autophosphorylation of two activation loop tyrosine RT residues."; RL J. Biol. Chem. 274:6453-6460(1999). RN [16] RP FUNCTION IN PHOSPHORYLATION OF PLCG1 AND PTK2/FAK1, INTERACTION WITH VEGFA, RP CATALYTIC ACTIVITY, PHOSPHORYLATION AT TYR-996; TYR-1054 AND TYR-1059, RP MUTAGENESIS OF TYR-996; TYR-1054 AND TYR-1059, SUBCELLULAR LOCATION, AND RP ACTIVITY REGULATION. RX PubMed=10102632; DOI=10.1038/sj.onc.1202478; RA Dougher M., Terman B.I.; RT "Autophosphorylation of KDR in the kinase domain is required for maximal RT VEGF-stimulated kinase activity and receptor internalization."; RL Oncogene 18:1619-1627(1999). RN [17] RP INTERACTION WITH HIV-1 TAT (MICROBIAL INFECTION). RX PubMed=10590123; DOI=10.1128/jvi.74.1.344-353.2000; RA Mitola S., Soldi R., Zanon I., Barra L., Gutierrez M.I., Berkhout B., RA Giacca M., Bussolino F.; RT "Identification of specific molecular structures of human immunodeficiency RT virus type 1 Tat relevant for its biological effects on vascular RT endothelial cells."; RL J. Virol. 74:344-353(2000). RN [18] RP FUNCTION IN ENDOTHELIAL CELL PROLIFERATION; PHOSPHORYLATION OF PLCG1 AND RP ACTIVATION OF MAP KINASES, PHOSPHORYLATION AT TYR-1175 AND TYR-1214, AND RP MUTAGENESIS OF LYS-868 AND TYR-1175. RX PubMed=11387210; DOI=10.1093/emboj/20.11.2768; RA Takahashi T., Yamaguchi S., Chida K., Shibuya M.; RT "A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A- RT dependent activation of PLC-gamma and DNA synthesis in vascular endothelial RT cells."; RL EMBO J. 20:2768-2778(2001). RN [19] RP UBIQUITINATION, FUNCTION IN NITRIC OXIDE PRODUCTION, SUBCELLULAR LOCATION, RP AND INTERACTION WITH CBL. RX PubMed=12649282; DOI=10.1074/jbc.m301410200; RA Duval M., Bedard-Goulet S., Delisle C., Gratton J.P.; RT "Vascular endothelial growth factor-dependent down-regulation of Flk-1/KDR RT involves Cbl-mediated ubiquitination. Consequences on nitric oxide RT production from endothelial cells."; RL J. Biol. Chem. 278:20091-20097(2003). RN [20] RP INTERACTION WITH FLT4. RX PubMed=12881528; DOI=10.1074/jbc.m304499200; RA Dixelius J., Makinen T., Wirzenius M., Karkkainen M.J., Wernstedt C., RA Alitalo K., Claesson-Welsh L.; RT "Ligand-induced vascular endothelial growth factor receptor-3 (VEGFR-3) RT heterodimerization with VEGFR-2 in primary lymphatic endothelial cells RT regulates tyrosine phosphorylation sites."; RL J. Biol. Chem. 278:40973-40979(2003). RN [21] RP INTERACTION WITH SHB, AND FUNCTION IN CELL MIGRATION. RX PubMed=15026417; DOI=10.1074/jbc.m312729200; RA Holmqvist K., Cross M.J., Rolny C., Haegerkvist R., Rahimi N., RA Matsumoto T., Claesson-Welsh L., Welsh M.; RT "The adaptor protein shb binds to tyrosine 1175 in vascular endothelial RT growth factor (VEGF) receptor-2 and regulates VEGF-dependent cellular RT migration."; RL J. Biol. Chem. 279:22267-22275(2004). RN [22] RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION. RX PubMed=14991896; DOI=10.1002/path.1520; RA Fox S.B., Turley H., Cheale M., Blazquez C., Roberts H., James N., Cook N., RA Harris A., Gatter K.; RT "Phosphorylated KDR is expressed in the neoplastic and stromal elements of RT human renal tumours and shuttles from cell membrane to nucleus."; RL J. Pathol. 202:313-320(2004). RN [23] RP INTERACTION WITH VEGFA AND VEGFD, PHOSPHORYLATION AT TYR-1054 AND TYR-1059, RP FUNCTION IN VEGFA AND VEGFD SIGNALING; ACTIVATION OF MAPK1/ERK2 AND RP MAPK3/ERK1; ACTIVATION OF AKT1; PHOSPHORYLATION OF PLCG1 AND NOS3; RP MODULATION OF INTRACELLULAR CA(2+) LEVELS; CELL SURVIVAL AND POSITIVE RP REGULATION OF CELL PROLIFERATION; CELL MIGRATION AND ANGIOGENESIS, AND RP ACTIVITY REGULATION. RX PubMed=15215251; DOI=10.1074/jbc.m401538200; RA Jia H., Bagherzadeh A., Bicknell R., Duchen M.R., Liu D., Zachary I.; RT "Vascular endothelial growth factor (VEGF)-D and VEGF-A differentially RT regulate KDR-mediated signaling and biological function in vascular RT endothelial cells."; RL J. Biol. Chem. 279:36148-36157(2004). RN [24] RP FUNCTION IN CELL MIGRATION; PHOSPHORYLATION OF PLCG1; ACTIVATION OF RP MAPK1/ERK2; MAPK3/ERK1 AND THE MAP KINASES AND IN REGULATION OF ACTIN RP CYTOSKELETON REORGANIZATION, INTERACTION WITH SH2D2A/TSAD, PHOSPHORYLATION RP AT TYR-951; TYR-1054; TYR-1059; TYR-1214; TYR-1305; TYR-1309 AND TYR-1319, RP AND MUTAGENESIS OF TYR-951. RX PubMed=15962004; DOI=10.1038/sj.emboj.7600709; RA Matsumoto T., Bohman S., Dixelius J., Berge T., Dimberg A., Magnusson P., RA Wang L., Wikner C., Qi J.H., Wernstedt C., Wu J., Bruheim S., Mugishima H., RA Mukhopadhyay D., Spurkland A., Claesson-Welsh L.; RT "VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in RT tumor angiogenesis."; RL EMBO J. 24:2342-2353(2005). RN [25] RP FUNCTION IN ENDOTHELIAL CELL MIGRATION; ACTIVATION OF MAP KINASES AND IN RP PHOSPHORYLATION OF FYN; SRC AND NCK1, INTERACTION WITH GRB2; FYN AND NCK1, RP AND MUTAGENESIS OF TYR-1214. RX PubMed=16966330; DOI=10.1074/jbc.m603928200; RA Lamalice L., Houle F., Huot J.; RT "Phosphorylation of Tyr1214 within VEGFR-2 triggers the recruitment of Nck RT and activation of Fyn leading to SAPK2/p38 activation and endothelial cell RT migration in response to VEGF."; RL J. Biol. Chem. 281:34009-34020(2006). RN [26] RP SUBCELLULAR LOCATION, UBIQUITINATION, AND DEGRADATION. RX PubMed=17004325; DOI=10.1111/j.1600-0854.2006.00462.x; RA Ewan L.C., Jopling H.M., Jia H., Mittar S., Bagherzadeh A., Howell G.J., RA Walker J.H., Zachary I.C., Ponnambalam S.; RT "Intrinsic tyrosine kinase activity is required for vascular endothelial RT growth factor receptor 2 ubiquitination, sorting and degradation in RT endothelial cells."; RL Traffic 7:1270-1282(2006). RN [27] RP FUNCTION IN ACTIVATION OF AKT1; PHOSPHORYLATION OF PLCG1 AND NOS3 AND RP REGULATION OF NITRIC OXIDE PRODUCTION, PHOSPHORYLATION AT TYR-801, AND RP MUTAGENESIS OF TYR-801. RX PubMed=17303569; DOI=10.1074/jbc.m609048200; RA Blanes M.G., Oubaha M., Rautureau Y., Gratton J.P.; RT "Phosphorylation of tyrosine 801 of vascular endothelial growth factor RT receptor-2 is necessary for Akt-dependent endothelial nitric-oxide synthase RT activation and nitric oxide release from endothelial cells."; RL J. Biol. Chem. 282:10660-10669(2007). RN [28] RP INTERACTION WITH DAB2IP. RX PubMed=19033661; DOI=10.1172/jci36168; RA Zhang H., He Y., Dai S., Xu Z., Luo Y., Wan T., Luo D., Jones D., Tang S., RA Chen H., Sessa W.C., Min W.; RT "AIP1 functions as an endogenous inhibitor of VEGFR2-mediated signaling and RT inflammatory angiogenesis in mice."; RL J. Clin. Invest. 118:3904-3916(2008). RN [29] RP PHOSPHORYLATION AT TYR-951; TYR-1175 AND TYR-1214, AND DEPHOSPHORYLATION BY RP PTPRB. RX PubMed=19136612; DOI=10.1096/fj.08-123810; RA Mellberg S., Dimberg A., Bahram F., Hayashi M., Rennel E., Ameur A., RA Westholm J.O., Larsson E., Lindahl P., Cross M.J., Claesson-Welsh L.; RT "Transcriptional profiling reveals a critical role for tyrosine phosphatase RT VE-PTP in regulation of VEGFR2 activity and endothelial cell RT morphogenesis."; RL FASEB J. 23:1490-1502(2009). RN [30] RP PHOSPHORYLATION AT TYR-801; TYR-951; TYR-996; TYR-1054; TYR-1059; TYR-1175 RP AND TYR-1214; DEPHOSPHORYLATION AT TYR-951; TYR-996; TYR-1054; TYR-1059; RP TYR-1175 AND TYR-1214 BY PTPRJ. RX PubMed=18936167; DOI=10.1128/mcb.01374-08; RA Chabot C., Spring K., Gratton J.P., Elchebly M., Royal I.; RT "New role for the protein tyrosine phosphatase DEP-1 in Akt activation and RT endothelial cell survival."; RL Mol. Cell. Biol. 29:241-253(2009). RN [31] RP FUNCTION AS VEGFA RECEPTOR IN TUMOR ANGIOGENESIS, SUBCELLULAR LOCATION, AND RP UBIQUITINATION. RX PubMed=19834490; DOI=10.1038/cdd.2009.152; RA Zhang Z., Neiva K.G., Lingen M.W., Ellis L.M., Nor J.E.; RT "VEGF-dependent tumor angiogenesis requires inverse and reciprocal RT regulation of VEGFR1 and VEGFR2."; RL Cell Death Differ. 17:499-512(2010). RN [32] RP FUNCTION IN LYMPHANGIOGENESIS (ISOFORM 2). RX PubMed=20179233; DOI=10.1158/1078-0432.ccr-09-1936; RA Becker J., Pavlakovic H., Ludewig F., Wilting F., Weich H.A., RA Albuquerque R., Ambati J., Wilting J.; RT "Neuroblastoma progression correlates with downregulation of the RT lymphangiogenesis inhibitor sVEGFR-2."; RL Clin. Cancer Res. 16:1431-1441(2010). RN [33] RP INTERACTION WITH VEGFC AND FLT4, SUBCELLULAR LOCATION, AND FUNCTION IN RP ANGIOGENESIS. RX PubMed=20224550; DOI=10.1038/emboj.2010.30; RA Nilsson I., Bahram F., Li X., Gualandi L., Koch S., Jarvius M., RA Soderberg O., Anisimov A., Kholova I., Pytowski B., Baldwin M., RA Yla-Herttuala S., Alitalo K., Kreuger J., Claesson-Welsh L.; RT "VEGF receptor 2/-3 heterodimers detected in situ by proximity ligation on RT angiogenic sprouts."; RL EMBO J. 29:1377-1388(2010). RN [34] RP SUBCELLULAR LOCATION. RX PubMed=21539813; DOI=10.1016/j.bbrc.2011.04.093; RA Jopling H.M., Howell G.J., Gamper N., Ponnambalam S.; RT "The VEGFR2 receptor tyrosine kinase undergoes constitutive endosome-to- RT plasma membrane recycling."; RL Biochem. Biophys. Res. Commun. 410:170-176(2011). RN [35] RP FUNCTION IN LYMPHANGIOGENESIS, AND INTERACTION WITH FLT4 AND VEGFC. RX PubMed=20705758; DOI=10.1182/blood-2010-02-267427; RA Nakao S., Zandi S., Hata Y., Kawahara S., Arita R., Schering A., Sun D., RA Melhorn M.I., Ito Y., Lara-Castillo N., Ishibashi T., Hafezi-Moghadam A.; RT "Blood vessel endothelial VEGFR-2 delays lymphangiogenesis: an endogenous RT trapping mechanism links lymph- and angiogenesis."; RL Blood 117:1081-1090(2011). RN [36] RP REVIEW ON ROLE IN ANGIOGENESIS. RX PubMed=17002866; DOI=10.5483/bmbrep.2006.39.5.469; RA Shibuya M.; RT "Differential roles of vascular endothelial growth factor receptor-1 and RT receptor-2 in angiogenesis."; RL J. Biochem. Mol. Biol. 39:469-478(2006). RN [37] RP REVIEW. RX PubMed=17658244; DOI=10.1016/j.cellsig.2007.05.013; RA Holmes K., Roberts O.L., Thomas A.M., Cross M.J.; RT "Vascular endothelial growth factor receptor-2: structure, function, RT intracellular signalling and therapeutic inhibition."; RL Cell. Signal. 19:2003-2012(2007). RN [38] RP REVIEW ON STRUCTURE AND FUNCTION. RX PubMed=18680722; DOI=10.1016/j.bbrc.2008.07.121; RA Roskoski R. Jr.; RT "VEGF receptor protein-tyrosine kinases: structure and regulation."; RL Biochem. Biophys. Res. Commun. 375:287-291(2008). RN [39] RP REVIEW ON ROLE IN ANGIOGENESIS AND CANCER. RX PubMed=19230644; DOI=10.1016/j.ceb.2008.12.012; RA Lohela M., Bry M., Tammela T., Alitalo K.; RT "VEGFs and receptors involved in angiogenesis versus lymphangiogenesis."; RL Curr. Opin. Cell Biol. 21:154-165(2009). RN [40] RP REVIEW ON LIGAND SPECIFICITY; FUNCTION; STRUCTURE; PHOSPHORYLATION AND RP SIGNALING. RX PubMed=19761875; DOI=10.1016/j.bbapap.2009.09.002; RA Grunewald F.S., Prota A.E., Giese A., Ballmer-Hofer K.; RT "Structure-function analysis of VEGF receptor activation and the role of RT coreceptors in angiogenic signaling."; RL Biochim. Biophys. Acta 1804:567-580(2010). RN [41] RP REVIEW ON ROLE IN ANGIOGENESIS AND CANCER. RX PubMed=20462514; DOI=10.1016/j.bbcan.2010.04.004; RA Guo S., Colbert L.S., Fuller M., Zhang Y., Gonzalez-Perez R.R.; RT "Vascular endothelial growth factor receptor-2 in breast cancer."; RL Biochim. Biophys. Acta 1806:108-121(2010). RN [42] RP REVIEW ON ROLE IN ANGIOGENESIS AND CANCER. RX PubMed=21779435; DOI=10.1177/1947601910392987; RA Shibuya M.; RT "Tyrosine kinase receptor Flt/VEGFR family: its characterization related to RT angiogenesis and cancer."; RL Genes Cancer 1:1119-1123(2010). RN [43] RP REVIEW ON LIGAND SPECIFICITY; FUNCTION; STRUCTURE; PHOSPHORYLATION AND RP SIGNALING. RX PubMed=21711246; DOI=10.1042/bj20110301; RA Koch S., Tugues S., Li X., Gualandi L., Claesson-Welsh L.; RT "Signal transduction by vascular endothelial growth factor receptors."; RL Biochem. J. 437:169-183(2011). RN [44] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-982 AND SER-984, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [45] RP FUNCTION, AND INTERACTION WITH PDCD6. RX PubMed=21893193; DOI=10.1016/j.cellsig.2011.08.013; RA Rho S.B., Song Y.J., Lim M.C., Lee S.H., Kim B.R., Park S.Y.; RT "Programmed cell death 6 (PDCD6) inhibits angiogenesis through RT PI3K/mTOR/p70S6K pathway by interacting of VEGFR-2."; RL Cell. Signal. 24:131-139(2012). RN [46] RP ACTIVITY REGULATION, REDOX-ACTIVE DISULFIDE BOND, AND MUTAGENESIS OF RP CYS-1045. RX PubMed=23199280; DOI=10.1089/ars.2012.4565; RA Tao B.B., Liu S.Y., Zhang C.C., Fu W., Cai W.J., Wang Y., Shen Q., RA Wang M.J., Chen Y., Zhang L.J., Zhu Y.Z., Zhu Y.C.; RT "VEGFR2 functions as an H(2)S-targeting receptor protein kinase with its RT novel Cys1045-Cys1024 disulfide bond serving as a specific molecular switch RT for hydrogen sulfide actions in vascular endothelial cells."; RL Antioxid. Redox Signal. 19:448-464(2013). RN [47] RP INTERACTION WITH ERN1, AND SUBCELLULAR LOCATION. RX PubMed=23529610; DOI=10.1161/circulationaha.112.001337; RA Zeng L., Xiao Q., Chen M., Margariti A., Martin D., Ivetic A., Xu H., RA Mason J., Wang W., Cockerill G., Mori K., Li J.Y., Chien S., Hu Y., Xu Q.; RT "Vascular endothelial cell growth-activated XBP1 splicing in endothelial RT cells is crucial for angiogenesis."; RL Circulation 127:1712-1722(2013). RN [48] RP INTERACTION WITH PDCL3. RX PubMed=23792958; DOI=10.1074/jbc.m113.473173; RA Srinivasan S., Meyer R.D., Lugo R., Rahimi N.; RT "Identification of PDCL3 as a novel chaperone protein involved in the RT generation of functional VEGF receptor 2."; RL J. Biol. Chem. 288:23171-23181(2013). RN [49] RP INTERACTION WITH CCDC88A. RX PubMed=25187647; DOI=10.1091/mbc.e14-05-0978; RA Lin C., Ear J., Midde K., Lopez-Sanchez I., Aznar N., Garcia-Marcos M., RA Kufareva I., Abagyan R., Ghosh P.; RT "Structural basis for activation of trimeric Gi proteins by multiple growth RT factor receptors via GIV/Girdin."; RL Mol. Biol. Cell 25:3654-3671(2014). RN [50] RP INTERACTION WITH PDCL3. RX PubMed=26059764; DOI=10.1007/s10456-015-9468-3; RA Srinivasan S., Chitalia V., Meyer R.D., Hartsough E., Mehta M., Harrold I., RA Anderson N., Feng H., Smith L.E., Jiang Y., Costello C.E., Rahimi N.; RT "Hypoxia-induced expression of phosducin-like 3 regulates expression of RT VEGFR-2 and promotes angiogenesis."; RL Angiogenesis 18:449-462(2015). RN [51] RP FUNCTION, INTERACTION WITH BSG, SUBCELLULAR LOCATION, SUBUNIT, AND RP PHOSPHORYLATION. RX PubMed=25825981; DOI=10.18632/oncotarget.2870; RA Khayati F., Perez-Cano L., Maouche K., Sadoux A., Boutalbi Z., RA Podgorniak M.P., Maskos U., Setterblad N., Janin A., Calvo F., Lebbe C., RA Menashi S., Fernandez-Recio J., Mourah S.; RT "EMMPRIN/CD147 is a novel coreceptor of VEGFR-2 mediating its activation by RT VEGF."; RL Oncotarget 6:9766-9780(2015). RN [52] RP INTERACTION WITH SLC31A1, AND DISULFIDE BOND. RX PubMed=35027734; DOI=10.1038/s41556-021-00822-7; RA Das A., Ash D., Fouda A.Y., Sudhahar V., Kim Y.M., Hou Y., Hudson F.Z., RA Stansfield B.K., Caldwell R.B., McMenamin M., Littlejohn R., Su H., RA Regan M.R., Merrill B.J., Poole L.B., Kaplan J.H., Fukai T., RA Ushio-Fukai M.; RT "Cysteine oxidation of copper transporter CTR1 drives VEGFR2 signalling and RT angiogenesis."; RL Nat. Cell Biol. 24:35-50(2022). RN [53] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 806-1171, FUNCTION, RP PHOSPHORYLATION AT TYR-1059, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=10368301; DOI=10.1016/s0969-2126(99)80042-2; RA McTigue M.A., Wickersham J.A., Pinko C., Showalter R.E., Parast C.V., RA Tempczyk-Russell A., Gehring M.R., Mroczkowski B., Kan C.-C., RA Villafranca J.E., Appelt K.; RT "Crystal structure of the kinase domain of human vascular endothelial RT growth factor receptor 2: a key enzyme in angiogenesis."; RL Structure 7:319-330(1999). RN [54] RP X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) OF 806-1171 IN COMPLEX WITH RP SYNTHETIC INHIBITOR. RX PubMed=15837294; DOI=10.1016/j.bmcl.2005.03.034; RA Miyazaki Y., Matsunaga S., Tang J., Maeda Y., Nakano M., Philippe R.J., RA Shibahara M., Liu W., Sato H., Wang L., Nolte R.T.; RT "Novel 4-amino-furo[2,3-d]pyrimidines as Tie-2 and VEGFR2 dual RT inhibitors."; RL Bioorg. Med. Chem. Lett. 15:2203-2207(2005). RN [55] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 815-1171 IN COMPLEX WITH RP SYNTHETIC INHIBITOR. RX PubMed=17253678; DOI=10.1021/jm061107l; RA Hodous B.L., Geuns-Meyer S.D., Hughes P.E., Albrecht B.K., Bellon S., RA Bready J., Caenepeel S., Cee V.J., Chaffee S.C., Coxon A., Emery M., RA Fretland J., Gallant P., Gu Y., Hoffman D., Johnson R.E., Kendall R., RA Kim J.L., Long A.M., Morrison M., Olivieri P.R., Patel V.F., Polverino A., RA Rose P., Tempest P., Wang L., Whittington D.A., Zhao H.; RT "Evolution of a highly selective and potent 2-(pyridin-2-yl)-1,3,5-triazine RT Tie-2 kinase inhibitor."; RL J. Med. Chem. 50:611-626(2007). RN [56] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 806-1171 IN COMPLEX WITH SYNTHETIC RP INHIBITOR, AND FUNCTION. RX PubMed=18529047; DOI=10.1021/jm8001185; RA Peifer C., Selig R., Kinkel K., Ott D., Totzke F., Schaechtele C., RA Heidenreich R., Roecken M., Schollmeyer D., Laufer S.; RT "Design, synthesis, and biological evaluation of novel 3-aryl-4-(1H-indole- RT 3yl)-1,5-dihydro-2H-pyrrole-2-ones as vascular endothelial growth factor RT receptor (VEGF-R) inhibitors."; RL J. Med. Chem. 51:3814-3824(2008). RN [57] RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 657-764, SUBUNIT, RP AUTOPHOSPHORYLATION, FUNCTION IN VEGFA SIGNALING AND ACTIVATION OF RP MAPK1/ERK2 AND MAPK3/ERK1, AND MUTAGENESIS OF ARG-726 AND ASP-731. RX PubMed=20080685; DOI=10.1073/pnas.0914052107; RA Yang Y., Xie P., Opatowsky Y., Schlessinger J.; RT "Direct contacts between extracellular membrane-proximal domains are RT required for VEGF receptor activation and cell signaling."; RL Proc. Natl. Acad. Sci. U.S.A. 107:1906-1911(2010). RN [58] RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 120-326 IN COMPLEX WITH VEGFC, RP INTERACTION WITH VEGFC, DOMAIN, DISULFIDE BONDS, AND GLYCOSYLATION AT RP ASN-143; ASN-245 AND ASN-318. RX PubMed=20145116; DOI=10.1073/pnas.0914318107; RA Leppanen V.M., Prota A.E., Jeltsch M., Anisimov A., Kalkkinen N., RA Strandin T., Lankinen H., Goldman A., Ballmer-Hofer K., Alitalo K.; RT "Structural determinants of growth factor binding and specificity by VEGF RT receptor 2."; RL Proc. Natl. Acad. Sci. U.S.A. 107:2425-2430(2010). RN [59] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 220-338 IN COMPLEX WITH ANTIBODY RP FRAGMENT, DISULFIDE BOND, AND GLYCOSYLATION AT ASN-245 AND ASN-318. RX PubMed=21827946; DOI=10.1016/j.str.2011.01.019; RA Franklin M.C., Navarro E.C., Wang Y., Patel S., Singh P., Zhang Y., RA Persaud K., Bari A., Griffith H., Shen L., Balderes P., Kussie P.; RT "The structural basis for the function of two anti-VEGF receptor 2 RT antibodies."; RL Structure 19:1097-1107(2011). RN [60] RP VARIANT HCI SER-1147. RX PubMed=11807987; DOI=10.1002/gcc.10028; RA Walter J.W., North P.E., Waner M., Mizeracki A., Blei F., Walker J.W.T., RA Reinisch J.F., Marchuk D.A.; RT "Somatic mutation of vascular endothelial growth factor receptors in RT juvenile hemangioma."; RL Genes Chromosomes Cancer 33:295-303(2002). RN [61] RP VARIANTS [LARGE SCALE ANALYSIS] LEU-275 AND ARG-873. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [62] RP VARIANTS [LARGE SCALE ANALYSIS] ARG-2; MET-136; GLY-248; ILE-297; VAL-462; RP HIS-472; ARG-482; ARG-539; MET-689; ASN-814 AND THR-1065. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [63] RP VARIANT ARG-482, AND INVOLVEMENT IN HCI. RX PubMed=18931684; DOI=10.1038/nm.1877; RA Jinnin M., Medici D., Park L., Limaye N., Liu Y., Boscolo E., Bischoff J., RA Vikkula M., Boye E., Olsen B.R.; RT "Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 RT signaling in infantile hemangioma."; RL Nat. Med. 14:1236-1246(2008). CC -!- FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor CC for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation CC of angiogenesis, vascular development, vascular permeability, and CC embryonic hematopoiesis. Promotes proliferation, survival, migration CC and differentiation of endothelial cells. Promotes reorganization of CC the actin cytoskeleton. Isoforms lacking a transmembrane domain, such CC as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, CC VEGFC and/or VEGFD. Isoform 2 plays an important role as negative CC regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting CC the amount of free VEGFA and/or VEGFC and preventing their binding to CC FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. CC Binding of vascular growth factors to isoform 1 leads to the activation CC of several signaling cascades. Activation of PLCG1 leads to the CC production of the cellular signaling molecules diacylglycerol and CC inositol 1,4,5-trisphosphate and the activation of protein kinase C. CC Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase CC signaling pathway, as well as of the AKT1 signaling pathway. Mediates CC phosphorylation of PIK3R1, the regulatory subunit of CC phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton CC and activation of PTK2/FAK1. Required for VEGFA-mediated induction of CC NOS2 and NOS3, leading to the production of the signaling molecule CC nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes CC phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC. CC {ECO:0000269|PubMed:10102632, ECO:0000269|PubMed:10368301, CC ECO:0000269|PubMed:10600473, ECO:0000269|PubMed:11387210, CC ECO:0000269|PubMed:12649282, ECO:0000269|PubMed:1417831, CC ECO:0000269|PubMed:15026417, ECO:0000269|PubMed:15215251, CC ECO:0000269|PubMed:15962004, ECO:0000269|PubMed:16966330, CC ECO:0000269|PubMed:17303569, ECO:0000269|PubMed:18529047, CC ECO:0000269|PubMed:19668192, ECO:0000269|PubMed:19834490, CC ECO:0000269|PubMed:20080685, ECO:0000269|PubMed:20224550, CC ECO:0000269|PubMed:20705758, ECO:0000269|PubMed:21893193, CC ECO:0000269|PubMed:25825981, ECO:0000269|PubMed:7929439, CC ECO:0000269|PubMed:9160888, ECO:0000269|PubMed:9804796, CC ECO:0000269|PubMed:9837777}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, CC ECO:0000269|PubMed:10037737, ECO:0000269|PubMed:10102632}; CC -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence CC of bound ligand. Binding of VEGFA, VEGFC or VEGFD leads to dimerization CC and activation by autophosphorylation on tyrosine residues. Inhibited CC by the small molecule PTK inhibitor SU5614 ((3Z)-5-Chloro-3-[(3,5- CC dimethyl-1H-pyrrol-2-yl)methylene]-1,3-dihydro-2H-indol-2-one). May be CC regulated by hydrogen sulfide (H(2)S) levels via a H(2)S-sensitive CC intracellular disulfide bond. {ECO:0000269|PubMed:10037737, CC ECO:0000269|PubMed:10102632, ECO:0000269|PubMed:15215251, CC ECO:0000269|PubMed:23199280}. CC -!- SUBUNIT: Homodimer in the presence of bound dimeric VEGFA, VEGFC or CC VEGFD ligands; monomeric in the absence of bound ligands. Can also form CC heterodimers with FLT1/VEGFR1 and KDR/VEGFR2. Interacts (tyrosine CC phosphorylated) with LFYN, NCK1, PLCG1. Interacts (tyrosine- CC phosphorylated active form preferentially) with DAB2IP (via C2 domain CC and active form preferentially); the interaction occurs at the late CC phase of VEGFA response and inhibits KDR/VEGFR2 activity. Interacts CC with SHBSH2D2A/TSAD, GRB2, MYOF, CBL and PDCD6. Interacts (via C- CC terminus domain) with ERN1 (via kinase domain); the interaction is CC facilitated in a XBP1 isoform 1- and vascular endothelial growth factor CC (VEGF)-dependent manner in endothelial cells (PubMed:23529610). CC Interacts (via juxtamembrane region) with chaperone PDCL3 (via CC thioredoxin fold region); the interaction leads to increased KDR/VEGFR2 CC abundance through inhibition of its ubiquitination and degradation CC (PubMed:23792958, PubMed:26059764). Interacts (tyrosine phosphorylated) CC with CCDC88A/GIV (via SH2-like region); binding requires CC autophosphorylation of the KDR/VEGFR2 C-terminal region CC (PubMed:25187647). Interacts with isoform 2 of BSG (PubMed:25825981). CC Interacts with SLC31A1; this interaction is induced upon VEGFA CC stimulation leading to SLC31A1 and KDR subsequent co-internalization to CC early endosomes, thereby activating KDR downstream signaling in CC endothelial cells (PubMed:35027734). {ECO:0000269|PubMed:10102632, CC ECO:0000269|PubMed:12649282, ECO:0000269|PubMed:12881528, CC ECO:0000269|PubMed:1417831, ECO:0000269|PubMed:15026417, CC ECO:0000269|PubMed:15215251, ECO:0000269|PubMed:15837294, CC ECO:0000269|PubMed:15962004, ECO:0000269|PubMed:16966330, CC ECO:0000269|PubMed:17253678, ECO:0000269|PubMed:18529047, CC ECO:0000269|PubMed:18593464, ECO:0000269|PubMed:19033661, CC ECO:0000269|PubMed:19668192, ECO:0000269|PubMed:20080685, CC ECO:0000269|PubMed:20145116, ECO:0000269|PubMed:20224550, CC ECO:0000269|PubMed:20705758, ECO:0000269|PubMed:21827946, CC ECO:0000269|PubMed:21893193, ECO:0000269|PubMed:23529610, CC ECO:0000269|PubMed:23792958, ECO:0000269|PubMed:25187647, CC ECO:0000269|PubMed:25825981, ECO:0000269|PubMed:26059764, CC ECO:0000269|PubMed:35027734, ECO:0000269|PubMed:9160888}. CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 Tat. CC {ECO:0000269|PubMed:10590123}. CC -!- INTERACTION: CC P35968; P35916: FLT4; NbExp=5; IntAct=EBI-1005487, EBI-1005467; CC P35968; O60565: GREM1; NbExp=4; IntAct=EBI-1005487, EBI-944395; CC P35968; P98160: HSPG2; NbExp=5; IntAct=EBI-1005487, EBI-947664; CC P35968; PRO_0000391621 [P98160]: HSPG2; NbExp=2; IntAct=EBI-1005487, EBI-6896259; CC P35968; PRO_0000391622 [P98160]: HSPG2; NbExp=2; IntAct=EBI-1005487, EBI-6896607; CC P35968; P17301: ITGA2; NbExp=2; IntAct=EBI-1005487, EBI-702960; CC P35968; P35968: KDR; NbExp=4; IntAct=EBI-1005487, EBI-1005487; CC P35968; P09382: LGALS1; NbExp=3; IntAct=EBI-1005487, EBI-1048875; CC P35968; P08581: MET; NbExp=3; IntAct=EBI-1005487, EBI-1039152; CC P35968; P16333: NCK1; NbExp=3; IntAct=EBI-1005487, EBI-389883; CC P35968; O14786: NRP1; NbExp=2; IntAct=EBI-1005487, EBI-1187100; CC P35968; O75340: PDCD6; NbExp=4; IntAct=EBI-1005487, EBI-352915; CC P35968; P09619: PDGFRB; NbExp=2; IntAct=EBI-1005487, EBI-641237; CC P35968; P29350: PTPN6; NbExp=2; IntAct=EBI-1005487, EBI-78260; CC P35968; Q12913: PTPRJ; NbExp=4; IntAct=EBI-1005487, EBI-2264500; CC P35968; P12931: SRC; NbExp=6; IntAct=EBI-1005487, EBI-621482; CC P35968; P15692: VEGFA; NbExp=5; IntAct=EBI-1005487, EBI-1026643; CC P35968; P15692-4: VEGFA; NbExp=8; IntAct=EBI-1005487, EBI-1026691; CC P35968; P49767: VEGFC; NbExp=6; IntAct=EBI-1005487, EBI-3405539; CC P35968; Q9MYV3-3: VEGFA; Xeno; NbExp=2; IntAct=EBI-1005487, EBI-15622828; CC -!- SUBCELLULAR LOCATION: Cell junction {ECO:0000250}. Endoplasmic CC reticulum {ECO:0000269|PubMed:23529610}. Cell membrane CC {ECO:0000269|PubMed:25825981}. Note=Localized with RAP1A at cell-cell CC junctions (By similarity). Colocalizes with ERN1 and XBP1 in the CC endoplasmic reticulum in endothelial cells in a vascular endothelial CC growth factor (VEGF)-dependent manner (PubMed:23529610). {ECO:0000250, CC ECO:0000269|PubMed:23529610}. CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I CC membrane protein. Cytoplasm. Nucleus. Cytoplasmic vesicle. Early CC endosome. Note=Detected on caveolae-enriched lipid rafts at the cell CC surface. Is recycled from the plasma membrane to endosomes and back CC again. Phosphorylation triggered by VEGFA binding promotes CC internalization and subsequent degradation. VEGFA binding triggers CC internalization and translocation to the nucleus. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=mbVegfr-2; CC IsoId=P35968-1; Sequence=Displayed; CC Name=2; Synonyms=sVegfr-2; CC IsoId=P35968-2; Sequence=VSP_041988, VSP_041989; CC Name=3; Synonyms=VEGFR2-712; CC IsoId=P35968-3; Sequence=VSP_041990, VSP_041991; CC -!- TISSUE SPECIFICITY: Detected in cornea (at protein level). Widely CC expressed. {ECO:0000269|PubMed:19668192}. CC -!- DOMAIN: The second and third Ig-like C2-type (immunoglobulin-like) CC domains are sufficient for VEGFC binding. CC {ECO:0000269|PubMed:20145116}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:20145116, CC ECO:0000269|PubMed:21827946, ECO:0000269|PubMed:9160888}. CC -!- PTM: Ubiquitinated. Tyrosine phosphorylation of the receptor promotes CC its poly-ubiquitination, leading to its degradation via the proteasome CC or lysosomal proteases. {ECO:0000269|PubMed:12649282, CC ECO:0000269|PubMed:17004325, ECO:0000269|PubMed:19834490}. CC -!- PTM: Autophosphorylated on tyrosine residues upon ligand binding. CC Autophosphorylation occurs in trans, i.e. one subunit of the dimeric CC receptor phosphorylates tyrosine residues on the other subunit. CC Phosphorylation at Tyr-951 is important for interaction with CC SH2D2A/TSAD and VEGFA-mediated reorganization of the actin CC cytoskeleton. Phosphorylation at Tyr-1175 is important for interaction CC with PLCG1 and SHB. Phosphorylation at Tyr-1214 is important for CC interaction with NCK1 and FYN. Dephosphorylated by PTPRB. CC Dephosphorylated by PTPRJ at Tyr-951, Tyr-996, Tyr-1054, Tyr-1059, Tyr- CC 1175 and Tyr-1214. {ECO:0000269|PubMed:10037737, CC ECO:0000269|PubMed:10102632, ECO:0000269|PubMed:10368301, CC ECO:0000269|PubMed:11387210, ECO:0000269|PubMed:15215251, CC ECO:0000269|PubMed:15962004, ECO:0000269|PubMed:18936167, CC ECO:0000269|PubMed:19136612, ECO:0000269|PubMed:25825981}. CC -!- PTM: The inhibitory disulfide bond between Cys-1024 and Cys-1045 may CC serve as a specific molecular switch for H(2)S-induced modification CC that regulates KDR/VEGFR2 function. CC -!- DISEASE: Hemangioma, capillary infantile (HCI) [MIM:602089]: A CC condition characterized by dull red, firm, dome-shaped hemangiomas, CC sharply demarcated from surrounding skin, usually presenting at birth CC or occurring within the first two or three months of life. They result CC from highly proliferative, localized growth of capillary endothelium CC and generally undergo regression and involution without scarring. CC {ECO:0000269|PubMed:11807987, ECO:0000269|PubMed:18931684}. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. CC -!- DISEASE: Note=Plays a major role in tumor angiogenesis. In case of HIV- CC 1 infection, the interaction with extracellular viral Tat protein seems CC to enhance angiogenesis in Kaposi's sarcoma lesions. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. CSF-1/PDGF receptor subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. 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; EU826563; ACF47599.1; -; mRNA. DR EMBL; FJ899739; ACR78514.1; -; mRNA. DR EMBL; AF035121; AAB88005.1; -; mRNA. DR EMBL; AF063658; AAC16450.1; -; mRNA. DR EMBL; AC021220; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC111194; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC131822; AAI31823.1; -; mRNA. DR EMBL; L04947; AAA59459.1; -; mRNA. DR EMBL; X61656; CAA43837.1; -; mRNA. DR EMBL; X89776; CAA61916.1; -; Genomic_DNA. DR CCDS; CCDS3497.1; -. [P35968-1] DR PIR; JC1402; JC1402. DR RefSeq; NP_002244.1; NM_002253.2. [P35968-1] DR PDB; 1VR2; X-ray; 2.40 A; A=806-1171. DR PDB; 1Y6A; X-ray; 2.10 A; A=806-1171. DR PDB; 1Y6B; X-ray; 2.10 A; A=806-1171. DR PDB; 1YWN; X-ray; 1.71 A; A=806-1171. DR PDB; 2M59; NMR; -; A/B=759-795. DR PDB; 2MET; NMR; -; A/B/C=759-795. DR PDB; 2MEU; NMR; -; A/B=759-795. DR PDB; 2OH4; X-ray; 2.05 A; A=806-1171. DR PDB; 2P2H; X-ray; 1.95 A; A=815-1171. DR PDB; 2P2I; X-ray; 2.40 A; A/B=815-1171. DR PDB; 2QU5; X-ray; 2.95 A; A=815-1171. DR PDB; 2QU6; X-ray; 2.10 A; A/B=815-1171. DR PDB; 2RL5; X-ray; 2.65 A; A=815-1171. DR PDB; 2X1W; X-ray; 2.70 A; L/M/N/O=120-326. DR PDB; 2X1X; X-ray; 3.10 A; R=120-326. DR PDB; 2XIR; X-ray; 1.50 A; A=806-1171. DR PDB; 3B8Q; X-ray; 2.75 A; A/B=815-1171. DR PDB; 3B8R; X-ray; 2.70 A; A/B=815-1171. DR PDB; 3BE2; X-ray; 1.75 A; A=815-1171. DR PDB; 3C7Q; X-ray; 2.10 A; A=806-1171. DR PDB; 3CJF; X-ray; 2.15 A; A=806-1168. DR PDB; 3CJG; X-ray; 2.25 A; A=806-1168. DR PDB; 3CP9; X-ray; 2.50 A; A/B=815-1171. DR PDB; 3CPB; X-ray; 2.70 A; A/B=815-1171. DR PDB; 3CPC; X-ray; 2.40 A; A/B=815-1171. DR PDB; 3DTW; X-ray; 2.90 A; A/B=815-1171. DR PDB; 3EFL; X-ray; 2.20 A; A/B=815-1171. DR PDB; 3EWH; X-ray; 1.60 A; A=815-1171. DR PDB; 3KVQ; X-ray; 2.70 A; A=657-764. DR PDB; 3S35; X-ray; 2.20 A; X=220-338. DR PDB; 3S36; X-ray; 3.20 A; X=220-338. DR PDB; 3S37; X-ray; 2.70 A; X=220-338. DR PDB; 3U6J; X-ray; 2.15 A; A=815-1171. DR PDB; 3V2A; X-ray; 3.20 A; R=2-764. DR PDB; 3V6B; X-ray; 3.20 A; R=132-548. DR PDB; 3VHE; X-ray; 1.55 A; A=811-1169. DR PDB; 3VHK; X-ray; 2.49 A; A=806-1171. DR PDB; 3VID; X-ray; 2.30 A; A=813-1168. DR PDB; 3VNT; X-ray; 1.64 A; A=806-1171. DR PDB; 3VO3; X-ray; 1.52 A; A=806-1171. DR PDB; 3WZD; X-ray; 1.57 A; A=814-1172. DR PDB; 3WZE; X-ray; 1.90 A; A=814-1172. DR PDB; 4AG8; X-ray; 1.95 A; A=806-1171. DR PDB; 4AGC; X-ray; 2.00 A; A=787-1171. DR PDB; 4AGD; X-ray; 2.81 A; A=787-1171. DR PDB; 4ASD; X-ray; 2.03 A; A=787-1171. DR PDB; 4ASE; X-ray; 1.83 A; A=787-1171. DR PDB; 5EW3; X-ray; 2.50 A; A/B=806-1171. DR PDB; 5OYJ; X-ray; 2.38 A; C/D=326-549. DR PDB; 6GQO; X-ray; 1.87 A; A=806-939, A=991-1171. DR PDB; 6GQP; X-ray; 2.09 A; A=806-1171. DR PDB; 6GQQ; X-ray; 1.52 A; A=806-939, A=991-1171. DR PDB; 6XVJ; X-ray; 1.78 A; A=806-1171. DR PDB; 6XVK; X-ray; 1.99 A; A=806-1171. DR PDBsum; 1VR2; -. DR PDBsum; 1Y6A; -. DR PDBsum; 1Y6B; -. DR PDBsum; 1YWN; -. DR PDBsum; 2M59; -. DR PDBsum; 2MET; -. DR PDBsum; 2MEU; -. DR PDBsum; 2OH4; -. DR PDBsum; 2P2H; -. DR PDBsum; 2P2I; -. DR PDBsum; 2QU5; -. DR PDBsum; 2QU6; -. DR PDBsum; 2RL5; -. DR PDBsum; 2X1W; -. DR PDBsum; 2X1X; -. DR PDBsum; 2XIR; -. DR PDBsum; 3B8Q; -. DR PDBsum; 3B8R; -. DR PDBsum; 3BE2; -. DR PDBsum; 3C7Q; -. DR PDBsum; 3CJF; -. DR PDBsum; 3CJG; -. DR PDBsum; 3CP9; -. DR PDBsum; 3CPB; -. DR PDBsum; 3CPC; -. DR PDBsum; 3DTW; -. DR PDBsum; 3EFL; -. DR PDBsum; 3EWH; -. DR PDBsum; 3KVQ; -. DR PDBsum; 3S35; -. DR PDBsum; 3S36; -. DR PDBsum; 3S37; -. DR PDBsum; 3U6J; -. DR PDBsum; 3V2A; -. DR PDBsum; 3V6B; -. DR PDBsum; 3VHE; -. DR PDBsum; 3VHK; -. DR PDBsum; 3VID; -. DR PDBsum; 3VNT; -. DR PDBsum; 3VO3; -. DR PDBsum; 3WZD; -. DR PDBsum; 3WZE; -. DR PDBsum; 4AG8; -. DR PDBsum; 4AGC; -. DR PDBsum; 4AGD; -. DR PDBsum; 4ASD; -. DR PDBsum; 4ASE; -. DR PDBsum; 5EW3; -. DR PDBsum; 5OYJ; -. DR PDBsum; 6GQO; -. DR PDBsum; 6GQP; -. DR PDBsum; 6GQQ; -. DR PDBsum; 6XVJ; -. DR PDBsum; 6XVK; -. DR AlphaFoldDB; P35968; -. DR BMRB; P35968; -. DR SMR; P35968; -. DR BioGRID; 109992; 131. DR CORUM; P35968; -. DR DIP; DIP-486N; -. DR IntAct; P35968; 224. DR MINT; P35968; -. DR STRING; 9606.ENSP00000263923; -. DR BindingDB; P35968; -. DR ChEMBL; CHEMBL279; -. DR DrugBank; DB04727; 1-{4-[4-Amino-6-(4-methoxyphenyl)furo[2,3-d]pyrimidin-5-yl]phenyl}-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea. DR DrugBank; DB07514; 3-(2-aminoquinazolin-6-yl)-1-(3,3-dimethylindolin-6-yl)-4-methylpyridin-2(1H)-one. DR DrugBank; DB07528; 3-(2-aminoquinazolin-6-yl)-4-methyl-1-[3-(trifluoromethyl)phenyl]pyridin-2(1H)-one. DR DrugBank; DB06938; 4-[[2-[[4-chloro-3-(trifluoromethyl)phenyl]amino]-3H-benzimidazol-5-yl]oxy]-N-methyl-pyridine-2-carboxamide. DR DrugBank; DB07326; 6-chloro-N-pyrimidin-5-yl-3-{[3-(trifluoromethyl)phenyl]amino}-1,2-benzisoxazole-7-carboxamide. DR DrugBank; DB06626; Axitinib. DR DrugBank; DB08875; Cabozantinib. DR DrugBank; DB04849; Cediranib. DR DrugBank; DB05198; CYC116. DR DrugBank; DB12147; Erdafitinib. DR DrugBank; DB12307; Foretinib. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB06101; IMC-1C11. DR DrugBank; DB09078; Lenvatinib. DR DrugBank; DB06080; Linifanib. DR DrugBank; DB06595; Midostaurin. DR DrugBank; DB07537; N'-(6-aminopyridin-3-yl)-N-(2-cyclopentylethyl)-4-methyl-benzene-1,3-dicarboxamide. DR DrugBank; DB07183; N-(4-phenoxyphenyl)-2-[(pyridin-4-ylmethyl)amino]nicotinamide. DR DrugBank; DB07333; N-(CYCLOPROPYLMETHYL)-4-(METHYLOXY)-3-({5-[3-(3-PYRIDINYL)PHENYL]-1,3-OXAZOL-2-YL}AMINO)BENZENESULFONAMIDE. DR DrugBank; DB07334; N-[5-(ETHYLSULFONYL)-2-METHOXYPHENYL]-5-[3-(2-PYRIDINYL)PHENYL]-1,3-OXAZOL-2-AMINE. DR DrugBank; DB07274; N-cyclopropyl-6-[(6,7-dimethoxyquinolin-4-yl)oxy]naphthalene-1-carboxamide. DR DrugBank; DB09079; Nintedanib. DR DrugBank; DB08519; N~4~-(3-methyl-1H-indazol-6-yl)-N~2~-(3,4,5-trimethoxyphenyl)pyrimidine-2,4-diamine. DR DrugBank; DB08042; N~4~-methyl-N~4~-(3-methyl-1H-indazol-6-yl)-N~2~-(3,4,5-trimethoxyphenyl)pyrimidine-2,4-diamine. DR DrugBank; DB16265; Olinvacimab. DR DrugBank; DB06589; Pazopanib. DR DrugBank; DB05931; Pegdinetanib. DR DrugBank; DB08901; Ponatinib. DR DrugBank; DB15822; Pralsetinib. DR DrugBank; DB05984; RAF-265. DR DrugBank; DB05578; Ramucirumab. DR DrugBank; DB08896; Regorafenib. DR DrugBank; DB14840; Ripretinib. DR DrugBank; DB06436; Semaxanib. DR DrugBank; DB00398; Sorafenib. DR DrugBank; DB01268; Sunitinib. DR DrugBank; DB05075; TG-100801. DR DrugBank; DB11800; Tivozanib. DR DrugBank; DB04879; Vatalanib. DR DrugBank; DB05146; XL820. DR DrugBank; DB05014; XL999. DR DrugCentral; P35968; -. DR GuidetoPHARMACOLOGY; 1813; -. DR CarbonylDB; P35968; -. DR GlyCosmos; P35968; 19 sites, 1 glycan. DR GlyGen; P35968; 22 sites, 2 O-linked glycans (3 sites). DR iPTMnet; P35968; -. DR PhosphoSitePlus; P35968; -. DR BioMuta; KDR; -. DR DMDM; 9087218; -. DR CPTAC; CPTAC-3120; -. DR EPD; P35968; -. DR jPOST; P35968; -. DR MassIVE; P35968; -. DR MaxQB; P35968; -. DR PaxDb; 9606-ENSP00000263923; -. DR PeptideAtlas; P35968; -. DR ProteomicsDB; 55169; -. [P35968-1] DR ProteomicsDB; 55170; -. [P35968-2] DR ProteomicsDB; 55171; -. [P35968-3] DR ABCD; P35968; 72 sequenced antibodies. DR Antibodypedia; 3413; 4235 antibodies from 53 providers. DR DNASU; 3791; -. DR Ensembl; ENST00000263923.5; ENSP00000263923.4; ENSG00000128052.10. [P35968-1] DR GeneID; 3791; -. DR KEGG; hsa:3791; -. DR MANE-Select; ENST00000263923.5; ENSP00000263923.4; NM_002253.4; NP_002244.1. DR UCSC; uc003has.4; human. [P35968-1] DR AGR; HGNC:6307; -. DR CTD; 3791; -. DR DisGeNET; 3791; -. DR GeneCards; KDR; -. DR HGNC; HGNC:6307; KDR. DR HPA; ENSG00000128052; Low tissue specificity. DR MalaCards; KDR; -. DR MIM; 191306; gene. DR MIM; 602089; phenotype. DR neXtProt; NX_P35968; -. DR OpenTargets; ENSG00000128052; -. DR Orphanet; 464293; NON RARE IN EUROPE: Infantile capillary hemangioma. DR Orphanet; 3303; Tetralogy of Fallot. DR PharmGKB; PA30086; -. DR VEuPathDB; HostDB:ENSG00000128052; -. DR eggNOG; KOG0200; Eukaryota. DR GeneTree; ENSGT00940000156710; -. DR HOGENOM; CLU_000288_49_4_1; -. DR InParanoid; P35968; -. DR OMA; FYRDTDM; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; P35968; -. DR TreeFam; TF325768; -. DR BRENDA; 2.7.10.1; 2681. DR PathwayCommons; P35968; -. DR Reactome; R-HSA-194306; Neurophilin interactions with VEGF and VEGFR. DR Reactome; R-HSA-195399; VEGF binds to VEGFR leading to receptor dimerization. DR Reactome; R-HSA-216083; Integrin cell surface interactions. DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway. DR Reactome; R-HSA-5218921; VEGFR2 mediated cell proliferation. DR Reactome; R-HSA-9673768; Signaling by membrane-tethered fusions of PDGFRA or PDGFRB. DR SignaLink; P35968; -. DR SIGNOR; P35968; -. DR BioGRID-ORCS; 3791; 9 hits in 1200 CRISPR screens. DR EvolutionaryTrace; P35968; -. DR GeneWiki; Kinase_insert_domain_receptor; -. DR GenomeRNAi; 3791; -. DR Pharos; P35968; Tclin. DR PRO; PR:P35968; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P35968; Protein. DR Bgee; ENSG00000128052; Expressed in germinal epithelium of ovary and 190 other cell types or tissues. DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell. DR GO; GO:0030054; C:cell junction; ISS:UniProtKB. DR GO; GO:0005769; C:early endosome; ISS:BHF-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005768; C:endosome; IDA:UniProtKB. DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0043235; C:receptor complex; IBA:GO_Central. DR GO; GO:0097443; C:sorting endosome; ISS:BHF-UCL. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0045296; F:cadherin binding; IPI:UniProtKB. DR GO; GO:0015026; F:coreceptor activity; IEA:Ensembl. DR GO; GO:0019838; F:growth factor binding; IPI:BHF-UCL. DR GO; GO:0051879; F:Hsp90 protein binding; TAS:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0005178; F:integrin binding; IPI:BHF-UCL. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; TAS:BHF-UCL. DR GO; GO:0038085; F:vascular endothelial growth factor binding; IPI:BHF-UCL. DR GO; GO:0005021; F:vascular endothelial growth factor receptor activity; IDA:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IBA:GO_Central. DR GO; GO:0060837; P:blood vessel endothelial cell differentiation; IEA:Ensembl. DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IMP:BHF-UCL. DR GO; GO:0055074; P:calcium ion homeostasis; IEA:Ensembl. DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; IMP:UniProtKB. DR GO; GO:0045165; P:cell fate commitment; IEA:Ensembl. DR GO; GO:0016477; P:cell migration; IBA:GO_Central. DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; ISS:BHF-UCL. DR GO; GO:1904881; P:cellular response to hydrogen sulfide; IDA:BHF-UCL. DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IDA:UniProtKB. DR GO; GO:0035162; P:embryonic hemopoiesis; ISS:UniProtKB. DR GO; GO:0003157; P:endocardium development; IEA:Ensembl. DR GO; GO:0045446; P:endothelial cell differentiation; IBA:GO_Central. DR GO; GO:0003158; P:endothelium development; ISS:UniProtKB. DR GO; GO:0002070; P:epithelial cell maturation; IEA:Ensembl. DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl. DR GO; GO:0001945; P:lymph vessel development; IEA:Ensembl. DR GO; GO:0010463; P:mesenchymal cell proliferation; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IDA:UniProtKB. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl. DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; ISS:BHF-UCL. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IMP:BHF-UCL. DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IEA:Ensembl. 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; IMP:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; 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; IMP:BHF-UCL. DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB. DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; IDA:BHF-UCL. DR GO; GO:0016239; P:positive regulation of macroautophagy; IGI:MGI. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB. DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IEA:Ensembl. DR GO; GO:0051901; P:positive regulation of mitochondrial depolarization; IGI:MGI. DR GO; GO:0090141; P:positive regulation of mitochondrial fission; IGI:MGI. DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; IDA:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProtKB. DR GO; GO:0050927; P:positive regulation of positive chemotaxis; IDA:BHF-UCL. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB. DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IEA:Ensembl. DR GO; GO:2001214; P:positive regulation of vasculogenesis; ISS:UniProtKB. DR GO; GO:0048597; P:post-embryonic camera-type eye morphogenesis; IEA:Ensembl. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:1903010; P:regulation of bone development; IEA:Ensembl. DR GO; GO:0008360; P:regulation of cell shape; IDA:BHF-UCL. DR GO; GO:1901532; P:regulation of hematopoietic progenitor cell differentiation; IEA:Ensembl. DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central. DR GO; GO:0071526; P:semaphorin-plexin signaling pathway; IEA:Ensembl. DR GO; GO:0072089; P:stem cell proliferation; IEA:Ensembl. DR GO; GO:0043129; P:surfactant homeostasis; IEA:Ensembl. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0036324; P:vascular endothelial growth factor receptor-2 signaling pathway; IMP:BHF-UCL. DR GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; IMP:BHF-UCL. DR GO; GO:0061042; P:vascular wound healing; IMP:BHF-UCL. DR GO; GO:0001570; P:vasculogenesis; ISS:UniProtKB. DR CDD; cd00096; Ig; 1. DR CDD; cd05862; IgI_VEGFR; 1. DR CDD; cd05864; IgI_VEGFR-2; 1. DR CDD; cd05103; PTKc_VEGFR2; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 7. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR013098; Ig_I-set. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR003598; Ig_sub2. DR InterPro; IPR013151; Immunoglobulin. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR001824; Tyr_kinase_rcpt_3_CS. DR InterPro; IPR041348; VEGFR-2_TMD. DR InterPro; IPR009136; VEGFR2_rcpt. DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1. DR PANTHER; PTHR24416:SF45; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 2; 1. DR Pfam; PF07679; I-set; 2. DR Pfam; PF00047; ig; 1. DR Pfam; PF13895; Ig_2; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF21339; VEGFR-1-like_Ig-like; 1. DR Pfam; PF17988; VEGFR-2_TMD; 1. DR PIRSF; PIRSF000615; TyrPK_CSF1-R; 1. DR PRINTS; PR01832; VEGFRECEPTOR. DR PRINTS; PR01834; VEGFRECEPTR2. DR SMART; SM00409; IG; 7. DR SMART; SM00408; IGc2; 5. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF48726; Immunoglobulin; 6. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50835; IG_LIKE; 5. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS00240; RECEPTOR_TYR_KIN_III; 1. DR Genevisible; P35968; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Angiogenesis; ATP-binding; KW Cell junction; Cell membrane; Cytoplasm; Cytoplasmic vesicle; KW Developmental protein; Differentiation; Disulfide bond; KW Endoplasmic reticulum; Endosome; Glycoprotein; Host-virus interaction; KW Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding; Nucleus; KW Phosphoprotein; Receptor; Reference proteome; Repeat; Secreted; Signal; KW Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; KW Ubl conjugation. FT SIGNAL 1..19 FT /evidence="ECO:0000255" FT CHAIN 20..1356 FT /note="Vascular endothelial growth factor receptor 2" FT /id="PRO_0000016771" FT TOPO_DOM 20..764 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 765..785 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 786..1356 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 46..110 FT /note="Ig-like C2-type 1" FT DOMAIN 141..207 FT /note="Ig-like C2-type 2" FT DOMAIN 224..320 FT /note="Ig-like C2-type 3" FT DOMAIN 328..414 FT /note="Ig-like C2-type 4" FT DOMAIN 421..548 FT /note="Ig-like C2-type 5" FT DOMAIN 551..660 FT /note="Ig-like C2-type 6" FT DOMAIN 667..753 FT /note="Ig-like C2-type 7" FT DOMAIN 834..1162 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1274..1318 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1292..1315 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 1028 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 840..848 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000305" FT BINDING 868 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000305" FT SITE 1175 FT /note="Interaction with SHB" FT /evidence="ECO:0000250" FT MOD_RES 801 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:17303569, FT ECO:0000269|PubMed:18936167" FT MOD_RES 951 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:15962004, FT ECO:0000269|PubMed:18936167, ECO:0000269|PubMed:19136612" FT MOD_RES 982 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 984 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 996 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:10102632, FT ECO:0000269|PubMed:18936167" FT MOD_RES 1054 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:10037737, FT ECO:0000269|PubMed:10102632, ECO:0000269|PubMed:15215251, FT ECO:0000269|PubMed:15962004, ECO:0000269|PubMed:18936167" FT MOD_RES 1059 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:10037737, FT ECO:0000269|PubMed:10102632, ECO:0000269|PubMed:10368301, FT ECO:0000269|PubMed:15215251, ECO:0000269|PubMed:15962004, FT ECO:0000269|PubMed:18936167" FT MOD_RES 1175 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:11387210, FT ECO:0000269|PubMed:18936167, ECO:0000269|PubMed:19136612" FT MOD_RES 1214 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:11387210, FT ECO:0000269|PubMed:15962004, ECO:0000269|PubMed:18936167, FT ECO:0000269|PubMed:19136612" FT MOD_RES 1231 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P35918" FT MOD_RES 1235 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P35918" FT MOD_RES 1238 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P35918" FT MOD_RES 1305 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:15962004" FT MOD_RES 1309 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:15962004" FT MOD_RES 1319 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:15962004" FT CARBOHYD 46 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 66 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 96 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 143 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20145116" FT CARBOHYD 158 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 245 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20145116, FT ECO:0000269|PubMed:21827946" FT CARBOHYD 318 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20145116, FT ECO:0000269|PubMed:21827946" FT CARBOHYD 374 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 395 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 511 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 523 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 580 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 613 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 619 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 631 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 675 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 704 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 721 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 53..103 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 150..200 FT DISULFID 246..307 FT DISULFID 445..530 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 571..642 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 688..737 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 1024..1045 FT /note="Redox-active" FT DISULFID 1208 FT /note="Interchain (with C-189 in SLC31A1)" FT /evidence="ECO:0000269|PubMed:35027734" FT VAR_SEQ 663..678 FT /note="ERVAPTITGNLENQTT -> GRETILDHCAEAVGMP (in isoform 2)" FT /evidence="ECO:0000303|PubMed:19668192" FT /id="VSP_041988" FT VAR_SEQ 679..1356 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:19668192" FT /id="VSP_041989" FT VAR_SEQ 712 FT /note="G -> E (in isoform 3)" FT /evidence="ECO:0000303|PubMed:18593464" FT /id="VSP_041990" FT VAR_SEQ 713..1356 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:18593464" FT /id="VSP_041991" FT VARIANT 2 FT /note="Q -> R (in a lung adenocarcinoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042053" FT VARIANT 136 FT /note="V -> M (in dbSNP:rs35636987)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042054" FT VARIANT 248 FT /note="A -> G (in a renal clear cell carcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042055" FT VARIANT 275 FT /note="R -> L (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036126" FT VARIANT 297 FT /note="V -> I (in dbSNP:rs2305948)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_022071" FT VARIANT 462 FT /note="L -> V (in dbSNP:rs56286620)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042056" FT VARIANT 472 FT /note="Q -> H (in dbSNP:rs1870377)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:17344846" FT /id="VAR_020353" FT VARIANT 482 FT /note="C -> R (probable risk factor for HCI; expression of FT FLT1 in hemangioma endothelial cells is markedly reduced FT and KDR activity is increased compared to controls; low FT FLT1 expression in hemangioma cells is caused by reduced FT activity of a pathway involving ITGB1, ANTXR1, KDR and FT NFATC2IP; the mutation predicts to result in FT loss-of-function and disruption of the normal association FT of these molecules; dbSNP:rs34231037)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:18931684" FT /id="VAR_042057" FT VARIANT 539 FT /note="G -> R (in dbSNP:rs55716939)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042058" FT VARIANT 689 FT /note="T -> M (in dbSNP:rs34038364)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042059" FT VARIANT 814 FT /note="D -> N (in dbSNP:rs35603373)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042060" FT VARIANT 848 FT /note="V -> E (strongly reduced autophosphorylation and FT kinase activity; dbSNP:rs1139776)" FT /evidence="ECO:0000269|PubMed:10037737, FT ECO:0000269|PubMed:1656371" FT /id="VAR_046679" FT VARIANT 873 FT /note="G -> R (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036127" FT VARIANT 952 FT /note="V -> I (in dbSNP:rs13129474)" FT /id="VAR_046680" FT VARIANT 1065 FT /note="A -> T (in dbSNP:rs56302315)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042061" FT VARIANT 1147 FT /note="P -> S (in HCI; somatic mutation; FT dbSNP:rs121917766)" FT /evidence="ECO:0000269|PubMed:11807987" FT /id="VAR_063147" FT MUTAGEN 726 FT /note="R->A: Strongly reduced autophosphorylation and FT activation of MAP kinases." FT /evidence="ECO:0000269|PubMed:20080685" FT MUTAGEN 731 FT /note="D->A: Strongly reduced autophosphorylation and FT activation of MAP kinases." FT /evidence="ECO:0000269|PubMed:20080685" FT MUTAGEN 801 FT /note="Y->F: Abolishes stimulation of nitric oxide FT synthesis." FT /evidence="ECO:0000269|PubMed:17303569" FT MUTAGEN 868 FT /note="K->M: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:11387210" FT MUTAGEN 951 FT /note="Y->F: Abolishes reorganization of the actin FT cytoskeleton and cell migration in response to VEGFA." FT /evidence="ECO:0000269|PubMed:15962004" FT MUTAGEN 996 FT /note="Y->F: Strongly reduced autophosphorylation. Reduces FT phosphorylation of PLCG1." FT /evidence="ECO:0000269|PubMed:10102632" FT MUTAGEN 1045 FT /note="C->A: Significantly higher kinase activity." FT /evidence="ECO:0000269|PubMed:23199280" FT MUTAGEN 1054 FT /note="Y->F: Strongly reduced autophosphorylation. FT Abolishes phosphorylation of downstream signaling proteins; FT when associated with F-1059." FT /evidence="ECO:0000269|PubMed:10102632" FT MUTAGEN 1059 FT /note="Y->F: Strongly reduced autophosphorylation. FT Abolishes phosphorylation of downstream signaling proteins; FT when associated with F-1054." FT /evidence="ECO:0000269|PubMed:10102632" FT MUTAGEN 1175 FT /note="Y->F: Abolishes phosphorylation of PLCG1 and MAP FT kinases in response to VEGFA." FT /evidence="ECO:0000269|PubMed:11387210" FT MUTAGEN 1214 FT /note="Y->F: Loss of phosphorylation site. Abolishes FT reorganization of the actin cytoskeleton in response to FT VEGFA." FT /evidence="ECO:0000269|PubMed:16966330" FT CONFLICT 2 FT /note="Q -> E (in Ref. 4; AAC16450)" FT /evidence="ECO:0000305" FT CONFLICT 772 FT /note="A -> T (in Ref. 7; AAA59459/CAA43837)" FT /evidence="ECO:0000305" FT CONFLICT 787 FT /note="R -> G (in Ref. 7; AAA59459/CAA43837)" FT /evidence="ECO:0000305" FT CONFLICT 835 FT /note="K -> N (in Ref. 7; AAA59459/CAA43837)" FT /evidence="ECO:0000305" FT CONFLICT 1347 FT /note="S -> T (in Ref. 7; AAA59459/CAA43837)" FT /evidence="ECO:0000305" FT STRAND 134..138 FT /evidence="ECO:0007829|PDB:2X1W" FT STRAND 145..148 FT /evidence="ECO:0007829|PDB:2X1W" FT STRAND 152..154 FT /evidence="ECO:0007829|PDB:2X1W" FT STRAND 159..164 FT /evidence="ECO:0007829|PDB:2X1W" FT TURN 165..167 FT /evidence="ECO:0007829|PDB:2X1W" FT STRAND 168..170 FT /evidence="ECO:0007829|PDB:2X1W" FT STRAND 174..176 FT /evidence="ECO:0007829|PDB:2X1W" FT STRAND 178..180 FT /evidence="ECO:0007829|PDB:2X1W" FT TURN 181..183 FT /evidence="ECO:0007829|PDB:2X1W" FT STRAND 184..188 FT /evidence="ECO:0007829|PDB:2X1W" FT HELIX 189..191 FT /evidence="ECO:0007829|PDB:2X1W" FT TURN 192..194 FT /evidence="ECO:0007829|PDB:2X1W" FT STRAND 196..202 FT /evidence="ECO:0007829|PDB:2X1W" FT STRAND 207..210 FT /evidence="ECO:0007829|PDB:3V2A" FT STRAND 214..218 FT /evidence="ECO:0007829|PDB:2X1W" FT STRAND 223..230 FT /evidence="ECO:0007829|PDB:3S35" FT STRAND 234..238 FT /evidence="ECO:0007829|PDB:3S35" FT STRAND 242..250 FT /evidence="ECO:0007829|PDB:3S35" FT STRAND 252..254 FT /evidence="ECO:0007829|PDB:3V6B" FT STRAND 257..261 FT /evidence="ECO:0007829|PDB:3S35" FT HELIX 269..272 FT /evidence="ECO:0007829|PDB:3S35" FT STRAND 273..276 FT /evidence="ECO:0007829|PDB:3V2A" FT STRAND 279..282 FT /evidence="ECO:0007829|PDB:3S35" FT STRAND 285..296 FT /evidence="ECO:0007829|PDB:3S35" FT HELIX 299..301 FT /evidence="ECO:0007829|PDB:3S35" FT STRAND 303..310 FT /evidence="ECO:0007829|PDB:3S35" FT STRAND 315..328 FT /evidence="ECO:0007829|PDB:3S35" FT STRAND 338..343 FT /evidence="ECO:0007829|PDB:5OYJ" FT STRAND 348..351 FT /evidence="ECO:0007829|PDB:5OYJ" FT STRAND 354..358 FT /evidence="ECO:0007829|PDB:5OYJ" FT STRAND 361..366 FT /evidence="ECO:0007829|PDB:5OYJ" FT STRAND 377..387 FT /evidence="ECO:0007829|PDB:5OYJ" FT HELIX 390..392 FT /evidence="ECO:0007829|PDB:5OYJ" FT STRAND 394..401 FT /evidence="ECO:0007829|PDB:5OYJ" FT TURN 403..405 FT /evidence="ECO:0007829|PDB:5OYJ" FT STRAND 408..425 FT /evidence="ECO:0007829|PDB:5OYJ" FT STRAND 434..436 FT /evidence="ECO:0007829|PDB:5OYJ" FT STRAND 441..451 FT /evidence="ECO:0007829|PDB:5OYJ" FT STRAND 454..462 FT /evidence="ECO:0007829|PDB:5OYJ" FT HELIX 463..465 FT /evidence="ECO:0007829|PDB:5OYJ" FT STRAND 482..484 FT /evidence="ECO:0007829|PDB:5OYJ" FT STRAND 497..499 FT /evidence="ECO:0007829|PDB:5OYJ" FT STRAND 503..507 FT /evidence="ECO:0007829|PDB:5OYJ" FT STRAND 510..521 FT /evidence="ECO:0007829|PDB:5OYJ" FT STRAND 526..534 FT /evidence="ECO:0007829|PDB:5OYJ" FT STRAND 537..548 FT /evidence="ECO:0007829|PDB:5OYJ" FT STRAND 676..679 FT /evidence="ECO:0007829|PDB:3KVQ" FT STRAND 684..687 FT /evidence="ECO:0007829|PDB:3KVQ" FT STRAND 697..706 FT /evidence="ECO:0007829|PDB:3KVQ" FT STRAND 713..716 FT /evidence="ECO:0007829|PDB:3KVQ" FT TURN 717..720 FT /evidence="ECO:0007829|PDB:3KVQ" FT STRAND 721..724 FT /evidence="ECO:0007829|PDB:3KVQ" FT HELIX 729..731 FT /evidence="ECO:0007829|PDB:3KVQ" FT STRAND 733..740 FT /evidence="ECO:0007829|PDB:3KVQ" FT STRAND 746..755 FT /evidence="ECO:0007829|PDB:3KVQ" FT HELIX 760..794 FT /evidence="ECO:0007829|PDB:2M59" FT STRAND 804..806 FT /evidence="ECO:0007829|PDB:4AGC" FT TURN 808..810 FT /evidence="ECO:0007829|PDB:4ASE" FT TURN 813..815 FT /evidence="ECO:0007829|PDB:3VHE" FT HELIX 817..819 FT /evidence="ECO:0007829|PDB:2XIR" FT HELIX 824..827 FT /evidence="ECO:0007829|PDB:2XIR" FT HELIX 831..833 FT /evidence="ECO:0007829|PDB:2XIR" FT STRAND 834..842 FT /evidence="ECO:0007829|PDB:2XIR" FT STRAND 844..858 FT /evidence="ECO:0007829|PDB:2XIR" FT STRAND 862..870 FT /evidence="ECO:0007829|PDB:2XIR" FT HELIX 876..892 FT /evidence="ECO:0007829|PDB:2XIR" FT STRAND 901..905 FT /evidence="ECO:0007829|PDB:2XIR" FT STRAND 907..910 FT /evidence="ECO:0007829|PDB:3WZD" FT STRAND 913..917 FT /evidence="ECO:0007829|PDB:2XIR" FT HELIX 924..929 FT /evidence="ECO:0007829|PDB:2XIR" FT TURN 930..933 FT /evidence="ECO:0007829|PDB:3VO3" FT STRAND 934..936 FT /evidence="ECO:0007829|PDB:2XIR" FT TURN 995..998 FT /evidence="ECO:0007829|PDB:3VO3" FT HELIX 1002..1021 FT /evidence="ECO:0007829|PDB:2XIR" FT STRAND 1024..1026 FT /evidence="ECO:0007829|PDB:4AGC" FT HELIX 1031..1033 FT /evidence="ECO:0007829|PDB:2XIR" FT STRAND 1034..1036 FT /evidence="ECO:0007829|PDB:2XIR" FT HELIX 1038..1040 FT /evidence="ECO:0007829|PDB:2XIR" FT STRAND 1042..1044 FT /evidence="ECO:0007829|PDB:2XIR" FT HELIX 1048..1050 FT /evidence="ECO:0007829|PDB:2XIR" FT TURN 1053..1055 FT /evidence="ECO:0007829|PDB:2XIR" FT STRAND 1059..1062 FT /evidence="ECO:0007829|PDB:2XIR" FT STRAND 1065..1067 FT /evidence="ECO:0007829|PDB:2XIR" FT HELIX 1069..1071 FT /evidence="ECO:0007829|PDB:2XIR" FT HELIX 1074..1079 FT /evidence="ECO:0007829|PDB:2XIR" FT HELIX 1084..1099 FT /evidence="ECO:0007829|PDB:2XIR" FT STRAND 1105..1108 FT /evidence="ECO:0007829|PDB:3C7Q" FT HELIX 1113..1121 FT /evidence="ECO:0007829|PDB:2XIR" FT HELIX 1133..1142 FT /evidence="ECO:0007829|PDB:2XIR" FT HELIX 1147..1149 FT /evidence="ECO:0007829|PDB:2XIR" FT HELIX 1153..1167 FT /evidence="ECO:0007829|PDB:2XIR" SQ SEQUENCE 1356 AA; 151527 MW; 59E7C44B05CFEBB3 CRC64; MQSKVLLAVA LWLCVETRAA SVGLPSVSLD LPRLSIQKDI LTIKANTTLQ ITCRGQRDLD WLWPNNQSGS EQRVEVTECS DGLFCKTLTI PKVIGNDTGA YKCFYRETDL ASVIYVYVQD YRSPFIASVS DQHGVVYITE NKNKTVVIPC LGSISNLNVS LCARYPEKRF VPDGNRISWD SKKGFTIPSY MISYAGMVFC EAKINDESYQ SIMYIVVVVG YRIYDVVLSP SHGIELSVGE KLVLNCTART ELNVGIDFNW EYPSSKHQHK KLVNRDLKTQ SGSEMKKFLS TLTIDGVTRS DQGLYTCAAS SGLMTKKNST FVRVHEKPFV AFGSGMESLV EATVGERVRI PAKYLGYPPP EIKWYKNGIP LESNHTIKAG HVLTIMEVSE RDTGNYTVIL TNPISKEKQS HVVSLVVYVP PQIGEKSLIS PVDSYQYGTT QTLTCTVYAI PPPHHIHWYW QLEEECANEP SQAVSVTNPY PCEEWRSVED FQGGNKIEVN KNQFALIEGK NKTVSTLVIQ AANVSALYKC EAVNKVGRGE RVISFHVTRG PEITLQPDMQ PTEQESVSLW CTADRSTFEN LTWYKLGPQP LPIHVGELPT PVCKNLDTLW KLNATMFSNS TNDILIMELK NASLQDQGDY VCLAQDRKTK KRHCVVRQLT VLERVAPTIT GNLENQTTSI GESIEVSCTA SGNPPPQIMW FKDNETLVED SGIVLKDGNR NLTIRRVRKE DEGLYTCQAC SVLGCAKVEA FFIIEGAQEK TNLEIIILVG TAVIAMFFWL LLVIILRTVK RANGGELKTG YLSIVMDPDE LPLDEHCERL PYDASKWEFP RDRLKLGKPL GRGAFGQVIE ADAFGIDKTA TCRTVAVKML KEGATHSEHR ALMSELKILI HIGHHLNVVN LLGACTKPGG PLMVIVEFCK FGNLSTYLRS KRNEFVPYKT KGARFRQGKD YVGAIPVDLK RRLDSITSSQ SSASSGFVEE KSLSDVEEEE APEDLYKDFL TLEHLICYSF QVAKGMEFLA SRKCIHRDLA ARNILLSEKN VVKICDFGLA RDIYKDPDYV RKGDARLPLK WMAPETIFDR VYTIQSDVWS FGVLLWEIFS LGASPYPGVK IDEEFCRRLK EGTRMRAPDY TTPEMYQTML DCWHGEPSQR PTFSELVEHL GNLLQANAQQ DGKDYIVLPI SETLSMEEDS GLSLPTSPVS CMEEEEVCDP KFHYDNTAGI SQYLQNSKRK SRPVSVKTFE DIPLEEPEVK VIPDDNQTDS GMVLASEELK TLEDRTKLSP SFGGMVPSKS RESVASEGSN QTSGYQSGYH SDDTDTTVYS SEEAELLKLI EIGVQTGSTA QILQPDSGTT LSSPPV //