VGFR2_HUMAN
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 03-AUG-2022, entry version 235.
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 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 [53]
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 [54]
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 [55]
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 [56]
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 [57]
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 [58]
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 [59]
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 [60]
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 [61]
RP VARIANT HCI ARG-482, AND VARIANTS [LARGE SCALE ANALYSIS] ARG-2; MET-136;
RP GLY-248; ILE-297; VAL-462; HIS-472; 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 [62]
RP VARIANT HCI ARG-482.
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 {ECO:0000269|PubMed:10102632, ECO:0000269|PubMed:12649282,
CC ECO:0000269|PubMed:12881528, ECO:0000269|PubMed:1417831,
CC ECO:0000269|PubMed:15026417, ECO:0000269|PubMed:15215251,
CC ECO:0000269|PubMed:15837294, ECO:0000269|PubMed:15962004,
CC ECO:0000269|PubMed:16966330, ECO:0000269|PubMed:17253678,
CC ECO:0000269|PubMed:18529047, ECO:0000269|PubMed:18593464,
CC ECO:0000269|PubMed:19033661, ECO:0000269|PubMed:19668192,
CC ECO:0000269|PubMed:20080685, ECO:0000269|PubMed:20145116,
CC ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20705758,
CC ECO:0000269|PubMed:21827946, ECO:0000269|PubMed:21893193,
CC ECO:0000269|PubMed:23529610, ECO:0000269|PubMed:23792958,
CC ECO:0000269|PubMed:25187647, ECO:0000269|PubMed:25825981,
CC ECO:0000269|PubMed:26059764, 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; O00629: KPNA4; NbExp=4; IntAct=EBI-1005487, EBI-396343;
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=6; 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:17344846,
CC ECO:0000269|PubMed:18931684}. Note=Disease susceptibility is associated
CC with variants affecting the 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}.
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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; 77.
DR CORUM; P35968; -.
DR DIP; DIP-486N; -.
DR IntAct; P35968; 174.
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; 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 GlyGen; P35968; 20 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P35968; -.
DR PhosphoSitePlus; P35968; -.
DR BioMuta; KDR; -.
DR DMDM; 9087218; -.
DR EPD; P35968; -.
DR jPOST; P35968; -.
DR MassIVE; P35968; -.
DR MaxQB; P35968; -.
DR PaxDb; P35968; -.
DR PeptideAtlas; P35968; -.
DR PRIDE; 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; 3684 antibodies from 52 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 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; RIFWDSK; -.
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 1116 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 188 other tissues.
DR Genevisible; P35968; HS.
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:0005887; C:integral component of plasma membrane; 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; IBA:GO_Central.
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:0070371; P:ERK1 and ERK2 cascade; IMP:BHF-UCL.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IBA:GO_Central.
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:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
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:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; 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:0043491; P:protein kinase B signaling; IMP:BHF-UCL.
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: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 Gene3D; 2.60.40.10; -; 7.
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; 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 Pfam; PF07679; I-set; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF17988; VEGFR-2_TMD; 1.
DR PRINTS; PR01834; VEGFRECEPTR2.
DR SMART; SM00409; IG; 7.
DR SMART; SM00408; IGc2; 5.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 6.
DR SUPFAM; SSF56112; SSF56112; 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.
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 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 (in HCI; associated with disease
FT susceptibility; expression of FLT1 in hemangioma
FT endothelial cells is markedly reduced and KDR activity is
FT increased compared to controls; low FLT1 expression in
FT hemangioma cells is caused by reduced activity of a pathway
FT involving ITGB1, ANTXR1, KDR and NFATC2IP; the mutation
FT predicts to result in loss-of-function and disruption of
FT the normal association of these molecules;
FT 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
