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Database: UniProt
Entry: VGFR3_HUMAN
LinkDB: VGFR3_HUMAN
Original site: VGFR3_HUMAN 
ID   VGFR3_HUMAN             Reviewed;        1363 AA.
AC   P35916; A8K6L4; B5A926; Q16067; Q86W07; Q86W08;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   16-NOV-2011, sequence version 3.
DT   24-JAN-2024, entry version 233.
DE   RecName: Full=Vascular endothelial growth factor receptor 3;
DE            Short=VEGFR-3;
DE            EC=2.7.10.1;
DE   AltName: Full=Fms-like tyrosine kinase 4;
DE            Short=FLT-4;
DE   AltName: Full=Tyrosine-protein kinase receptor FLT4;
DE   Flags: Precursor;
GN   Name=FLT4; Synonyms=VEGFR3;
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 2), AND TISSUE SPECIFICITY.
RX   PubMed=1327515;
RA   Pajusola K., Aprelikova O., Korhonen J., Kaipainen A., Pertovaara L.,
RA   Alitalo R., Alitalo K.;
RT   "FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and
RT   is expressed in multiple human tissues and cell lines.";
RL   Cancer Res. 52:5738-5743(1992).
RN   [2]
RP   ERRATUM OF PUBMED:1327515.
RA   Pajusola K., Aprelikova O., Korhonen J., Kaipainen A., Pertovaara L.,
RA   Alitalo R., Alitalo K.;
RL   Cancer Res. 53:3845-3845(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX   PubMed=1319394; DOI=10.1016/0888-7543(92)90277-y;
RA   Galland F., Karamysheva A., Mattei M.-G., Rosnet O., Marchetto S.,
RA   Birnbaum D.;
RT   "Chromosomal localization of FLT4, a novel receptor-type tyrosine kinase
RT   gene.";
RL   Genomics 13:475-478(1992).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS GLN-890 AND HIS-1146.
RC   TISSUE=Placenta;
RX   PubMed=8386825;
RA   Galland F., Karamysheva A., Pebusque M.-J., Borg J.-P., Rottapel R.,
RA   Dubreuil P., Rosnet O., Birnbaum D.;
RT   "The FLT4 gene encodes a transmembrane tyrosine kinase related to the
RT   vascular endothelial growth factor receptor.";
RL   Oncogene 8:1233-1240(1993).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH VEGFC,
RP   PHOSPHORYLATION, AND FUNCTION IN CELL PROLIFERATION.
RX   PubMed=8700872; DOI=10.1073/pnas.93.5.1988;
RA   Lee J., Gray A., Yuan J., Luoh S.-M., Avraham H., Wood W.I.;
RT   "Vascular endothelial growth factor-related protein: a ligand and specific
RT   activator of the tyrosine kinase receptor Flt4.";
RL   Proc. Natl. Acad. Sci. U.S.A. 93:1988-1992(1996).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), INTERACTION WITH VEGFD, 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   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANTS GLN-890 AND
RP   HIS-1146.
RA   Lian Z., Feitelson M.;
RL   Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLN-890.
RC   TISSUE=Placenta;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA   Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA   Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA   Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA   Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA   Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA   Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 761-1190.
RX   PubMed=1310071;
RA   Aprelikova O., Pajusola K., Partanen J., Armstrong E., Alitalo R.,
RA   Bailey S.K., McMahon J., Wasmuth J., Huebner K., Alitalo K.;
RT   "FLT4, a novel class III receptor tyrosine kinase in chromosome 5q33-
RT   qter.";
RL   Cancer Res. 52:746-748(1992).
RN   [11]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1293-1363 (ISOFORM 1), AND ALTERNATIVE
RP   SPLICING.
RX   PubMed=7692369;
RA   Pajusola K., Aprelikova O., Armstrong E., Morris S., Alitalo K.;
RT   "Two human FLT4 receptor tyrosine kinase isoforms with distinct carboxy
RT   terminal tails are produced by alternative processing of primary
RT   transcripts.";
RL   Oncogene 8:2931-2937(1993).
RN   [12]
RP   PROTEIN SEQUENCE OF 25-39.
RX   PubMed=15340161; DOI=10.1110/ps.04682504;
RA   Zhang Z., Henzel W.J.;
RT   "Signal peptide prediction based on analysis of experimentally verified
RT   cleavage sites.";
RL   Protein Sci. 13:2819-2824(2004).
RN   [13]
RP   CATALYTIC ACTIVITY, GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RX   PubMed=7898938;
RA   Borg J.P., deLapeyriere O., Noguchi T., Rottapel R., Dubreuil P.,
RA   Birnbaum D.;
RT   "Biochemical characterization of two isoforms of FLT4, a VEGF receptor-
RT   related tyrosine kinase.";
RL   Oncogene 10:973-984(1995).
RN   [14]
RP   FUNCTION IN CELL PROLIFERATION AND PHOSPHORYLATION OF SHC1,
RP   CHARACTERIZATION OF ISOFORM 1 AND ISOFORM 2, INTERACTION WITH SHC1 AND
RP   GRB2, AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-1333; TYR-1337 AND TYR-1363,
RP   AND TISSUE SPECIFICITY.
RX   PubMed=7675451;
RA   Fournier E., Dubreuil P., Birnbaum D., Borg J.P.;
RT   "Mutation at tyrosine residue 1337 abrogates ligand-dependent transforming
RT   capacity of the FLT4 receptor.";
RL   Oncogene 11:921-931(1995).
RN   [15]
RP   INTERACTION WITH VEGFD, FUNCTION AS VEGFD RECEPTOR, AND
RP   AUTOPHOSPHORYLATION.
RX   PubMed=9435229; DOI=10.1073/pnas.95.2.548;
RA   Achen M.G., Jeltsch M., Kukk E., Maekinen T., Vitali A., Wilks A.F.,
RA   Alitalo K., Stacker S.A.;
RT   "Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine
RT   kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4).";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:548-553(1998).
RN   [16]
RP   FUNCTION AS RECEPTOR FOR VEGFC AND VEGFD IN CELL SURVIVAL; PROLIFERATION
RP   AND MIGRATION, AND FUNCTION IN ACTIVATION OF PROTEIN KINASE C; AKT1;
RP   PIK3R1; MAPK1/ERK2 AND MAPK3/ERK1.
RX   PubMed=11532940; DOI=10.1093/emboj/20.17.4762;
RA   Makinen T., Veikkola T., Mustjoki S., Karpanen T., Catimel B., Nice E.C.,
RA   Wise L., Mercer A., Kowalski H., Kerjaschki D., Stacker S.A., Achen M.G.,
RA   Alitalo K.;
RT   "Isolated lymphatic endothelial cells transduce growth, survival and
RT   migratory signals via the VEGF-C/D receptor VEGFR-3.";
RL   EMBO J. 20:4762-4773(2001).
RN   [17]
RP   INTERACTION WITH KDR, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION,
RP   CHARACTERIZATION OF VARIANT LMPHM1 PRO-1041, MUTAGENESIS OF LYS-879;
RP   TYR-1230; TYR-1231; TYR-1265; TYR-1333; TYR-1337 AND TYR-1363, AND
RP   PHOSPHORYLATION AT TYR-1230; TYR-1231; TYR-1265; TYR-1333; TYR-1337 AND
RP   TYR-1363.
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   [18]
RP   FUNCTION IN KDR SIGNALING AND IN ANGIOGENESIS, INTERACTION WITH KDR, AND
RP   PHOSPHORYLATION.
RX   PubMed=15474514; DOI=10.1016/j.bbrc.2004.08.237;
RA   Alam A., Herault J.P., Barron P., Favier B., Fons P., Delesque-Touchard N.,
RA   Senegas I., Laboudie P., Bonnin J., Cassan C., Savi P., Ruggeri B.,
RA   Carmeliet P., Bono F., Herbert J.M.;
RT   "Heterodimerization with vascular endothelial growth factor receptor-2
RT   (VEGFR-2) is necessary for VEGFR-3 activity.";
RL   Biochem. Biophys. Res. Commun. 324:909-915(2004).
RN   [19]
RP   FUNCTION IN CELL SURVIVAL, PHOSPHORYLATION IN RESPONSE TO OXIDATIVE STRESS,
RP   INTERACTION WITH PIK3R1; SHC1; GRB2; PTPN11 AND PLCG1, ACTIVITY REGULATION
RP   BY MAZ51, AND CHARACTERIZATION OF VARIANT LMPHM1 ARG-857.
RX   PubMed=15102829; DOI=10.1074/jbc.m314015200;
RA   Wang J.F., Zhang X., Groopman J.E.;
RT   "Activation of vascular endothelial growth factor receptor-3 and its
RT   downstream signaling promote cell survival under oxidative stress.";
RL   J. Biol. Chem. 279:27088-27097(2004).
RN   [20]
RP   FUNCTION IN ACTIVATION OF AKT1; MAPK1/ERK2; MAPK3/ERK1 AND MAPK8, FUNCTION
RP   IN PROMOTING CELL SURVIVAL; PROLIFERATION AND MIGRATION, CHARACTERIZATION
RP   OF ISOFORM 1 AND ISOFORM 2, INTERACTION WITH CRK AND GRB2, PHOSPHORYLATION
RP   AT TYR-1063; TYR-1068; TYR-1230; TYR-1231 AND TYR-1337, AND MUTAGENESIS OF
RP   TYR-1063; TYR-1068; TYR-1230 AND TYR-1231.
RX   PubMed=16076871; DOI=10.1182/blood-2005-04-1388;
RA   Salameh A., Galvagni F., Bardelli M., Bussolino F., Oliviero S.;
RT   "Direct recruitment of CRK and GRB2 to VEGFR-3 induces proliferation,
RT   migration, and survival of endothelial cells through the activation of ERK,
RT   AKT, and JNK pathways.";
RL   Blood 106:3423-3431(2005).
RN   [21]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-527.
RC   TISSUE=Plasma;
RX   PubMed=16335952; DOI=10.1021/pr0502065;
RA   Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA   Smith R.D.;
RT   "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT   hydrazide chemistry, and mass spectrometry.";
RL   J. Proteome Res. 4:2070-2080(2005).
RN   [22]
RP   FUNCTION IN PROMOTING CELL SURVIVAL, INTERACTION WITH PTK2/FAK1, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=16452200; DOI=10.1158/0008-5472.can-05-1661;
RA   Garces C.A., Kurenova E.V., Golubovskaya V.M., Cance W.G.;
RT   "Vascular endothelial growth factor receptor-3 and focal adhesion kinase
RT   bind and suppress apoptosis in breast cancer cells.";
RL   Cancer Res. 66:1446-1454(2006).
RN   [23]
RP   FUNCTION IN LYMPHANGIOGENESIS.
RX   PubMed=17210781; DOI=10.1096/fj.06-6656com;
RA   Goldman J., Rutkowski J.M., Shields J.D., Pasquier M.C., Cui Y.,
RA   Schmokel H.G., Willey S., Hicklin D.J., Pytowski B., Swartz M.A.;
RT   "Cooperative and redundant roles of VEGFR-2 and VEGFR-3 signaling in adult
RT   lymphangiogenesis.";
RL   FASEB J. 21:1003-1012(2007).
RN   [24]
RP   ROLE IN CANCER, FUNCTION AS VEGFC RECEPTOR IN TUMOR LYMPHANGIOGENESIS; CELL
RP   PROLIFERATION; CELL SURVIVAL; IN ACTIVATION OF PIK3R1; AKT1 AND MAP KINASES
RP   AND IN UP-REGULATION OF VEGFA AND VEGFC EXPRESSION, ACTIVITY REGULATION,
RP   AND AUTOPHOSPHORYLATION.
RX   PubMed=19779139; DOI=10.2353/ajpath.2009.081139;
RA   Matsuura M., Onimaru M., Yonemitsu Y., Suzuki H., Nakano T., Ishibashi H.,
RA   Shirasuna K., Sueishi K.;
RT   "Autocrine loop between vascular endothelial growth factor (VEGF)-C and
RT   VEGF receptor-3 positively regulates tumor-associated lymphangiogenesis in
RT   oral squamoid cancer cells.";
RL   Am. J. Pathol. 175:1709-1721(2009).
RN   [25]
RP   ROLE IN CANCER, AND INTERACTION WITH PTK2/FAK1.
RX   PubMed=19610651; DOI=10.1021/jm900159g;
RA   Kurenova E.V., Hunt D.L., He D., Magis A.T., Ostrov D.A., Cance W.G.;
RT   "Small molecule chloropyramine hydrochloride (C4) targets the binding site
RT   of focal adhesion kinase and vascular endothelial growth factor receptor 3
RT   and suppresses breast cancer growth in vivo.";
RL   J. Med. Chem. 52:4716-4724(2009).
RN   [26]
RP   INTERACTION WITH PTPN14.
RX   PubMed=20826270; DOI=10.1016/j.ajhg.2010.08.008;
RA   Au A.C., Hernandez P.A., Lieber E., Nadroo A.M., Shen Y.M., Kelley K.A.,
RA   Gelb B.D., Diaz G.A.;
RT   "Protein tyrosine phosphatase PTPN14 is a regulator of lymphatic function
RT   and choanal development in humans.";
RL   Am. J. Hum. Genet. 87:436-444(2010).
RN   [27]
RP   PHOSPHORYLATION AT TYR-830; TYR-833; TYR-853; TYR-1063; TYR-1068; TYR-1333
RP   AND TYR-1337, IDENTIFICATION IN A COMPLEX WITH SRC AND ITGB1, MUTAGENESIS
RP   OF TYR-1063; TYR-1068 AND TYR-1337, ACTIVITY REGULATION BY MAZ51,
RP   INTERACTION WITH ITGB1; CRK AND SHC1, FUNCTION IN ACTIVATION OF MAPK8 AND
RP   IN REGULATION OF ANGIOGENIC SPROUTING, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RX   PubMed=20431062; DOI=10.1161/circresaha.109.206326;
RA   Galvagni F., Pennacchini S., Salameh A., Rocchigiani M., Neri F.,
RA   Orlandini M., Petraglia F., Gotta S., Sardone G.L., Matteucci G.,
RA   Terstappen G.C., Oliviero S.;
RT   "Endothelial cell adhesion to the extracellular matrix induces c-Src-
RT   dependent VEGFR-3 phosphorylation without the activation of the receptor
RT   intrinsic kinase activity.";
RL   Circ. Res. 106:1839-1848(2010).
RN   [28]
RP   INTERACTION WITH KDR, FUNCTION IN MODULATING KDR SIGNALING AND IN
RP   ANGIOGENESIS, AND TISSUE SPECIFICITY.
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   [29]
RP   FUNCTION IN ACTIVATION OF SIGNALING PATHWAYS, AND SUBCELLULAR LOCATION.
RX   PubMed=20445537; DOI=10.1038/nature09002;
RA   Wang Y., Nakayama M., Pitulescu M.E., Schmidt T.S., Bochenek M.L.,
RA   Sakakibara A., Adams S., Davy A., Deutsch U., Luthi U., Barberis A.,
RA   Benjamin L.E., Makinen T., Nobes C.D., Adams R.H.;
RT   "Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis.";
RL   Nature 465:483-486(2010).
RN   [30]
RP   FUNCTION IN LYMPHANGIOGENESIS.
RX   PubMed=21273538; DOI=10.1167/iovs.10-6408;
RA   Yuen D., Pytowski B., Chen L.;
RT   "Combined blockade of VEGFR-2 and VEGFR-3 inhibits inflammatory
RT   lymphangiogenesis in early and middle stages.";
RL   Invest. Ophthalmol. Vis. Sci. 52:2593-2597(2011).
RN   [31]
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   [32]
RP   REVIEW ON ROLE IN LYMPHANGIOGENESIS 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   [33]
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   [34]
RP   REVIEW ON FUNCTION IN LYMPHANGIOGENESIS AND ROLE IN CANCER.
RX   PubMed=21196198; DOI=10.2741/3715;
RA   Al-Rawi M.A., Jiang W.G.;
RT   "Lymphangiogenesis and cancer metastasis.";
RL   Front. Biosci. 16:723-739(2011).
RN   [35]
RP   X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 23-229 AND 330-553 IN COMPLEX
RP   WITH VEGFC, GLYCOSYLATION AT ASN-33; ASN-104; ASN-166; ASN-411 AND ASN-515,
RP   DISULFIDE BOND, INTERACTION WITH VEGFC, MUTAGENESIS OF THR-446; LYS-516 AND
RP   ARG-737, AUTOPHOSPHORYLATION, HOMODIMER, AND DOMAIN.
RX   PubMed=23878260; DOI=10.1073/pnas.1301415110;
RA   Leppanen V.M., Tvorogov D., Kisko K., Prota A.E., Jeltsch M., Anisimov A.,
RA   Markovic-Mueller S., Stuttfeld E., Goldie K.N., Ballmer-Hofer K.,
RA   Alitalo K.;
RT   "Structural and mechanistic insights into VEGF receptor 3 ligand binding
RT   and activation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 110:12960-12965(2013).
RN   [36]
RP   VARIANT LMPHM1 LEU-1114.
RX   PubMed=9817924; DOI=10.1093/hmg/7.13.2073;
RA   Ferrell R.E., Levinson K.L., Esman J.H., Kimak M.A., Lawrence E.C.,
RA   Barmada M.M., Finegold D.N.;
RT   "Hereditary lymphedema: evidence for linkage and genetic heterogeneity.";
RL   Hum. Mol. Genet. 7:2073-2078(1998).
RN   [37]
RP   INVOLVEMENT IN LMPHM1, AND CHARACTERIZATION OF VARIANT LMPHM1 ARG-1035.
RX   PubMed=10856194; DOI=10.1086/303019;
RA   Irrthum A., Karkkainen M.J., Devriendt K., Alitalo K., Vikkula M.;
RT   "Congenital hereditary lymphedema caused by a mutation that inactivates
RT   VEGFR3 tyrosine kinase.";
RL   Am. J. Hum. Genet. 67:295-301(2000).
RN   [38]
RP   VARIANTS LMPHM1 ARG-857; PRO-1041; PRO-1044 AND LEU-1114, VARIANT SER-641,
RP   AND CHARACTERIZATION OF VARIANTS.
RX   PubMed=10835628; DOI=10.1038/75997;
RA   Karkkainen M.J., Ferrell R.E., Lawrence E.C., Kimak M.A., Levinson K.L.,
RA   McTigue M.A., Alitalo K., Finegold D.N.;
RT   "Missense mutations interfere with VEGFR-3 signalling in primary
RT   lymphoedema.";
RL   Nat. Genet. 25:153-159(2000).
RN   [39]
RP   VARIANTS HCI SER-954 AND SER-1137, AND VARIANTS ALA-494; GLN-890 AND
RP   HIS-1146.
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   [40]
RP   VARIANTS LMPHM1 MET-878; THR-1086 AND PHE-1108 DEL, VARIANT GLN-1035, AND
RP   INVOLVEMENT IN LMPHM1.
RX   PubMed=16965327; DOI=10.1111/j.1399-0004.2006.00687.x;
RA   Ghalamkarpour A., Morlot S., Raas-Rothschild A., Utkus A., Mulliken J.B.,
RA   Boon L.M., Vikkula M.;
RT   "Hereditary lymphedema type I associated with VEGFR3 mutation: the first de
RT   novo case and atypical presentations.";
RL   Clin. Genet. 70:330-335(2006).
RN   [41]
RP   VARIANT LMPHM1 LYS-1106, AND INVOLVEMENT IN LMPHM1.
RX   PubMed=16924388; DOI=10.1007/s10038-006-0031-3;
RA   Spiegel R., Ghalamkarpour A., Daniel-Spiegel E., Vikkula M., Shalev S.A.;
RT   "Wide clinical spectrum in a family with hereditary lymphedema type I due
RT   to a novel missense mutation in VEGFR3.";
RL   J. Hum. Genet. 51:846-850(2006).
RN   [42]
RP   VARIANT LMPHM1 LEU-1020.
RX   PubMed=17458866; DOI=10.1002/ajmg.a.31703;
RA   Butler M.G., Dagenais S.L., Rockson S.G., Glover T.W.;
RT   "A novel VEGFR3 mutation causes Milroy disease.";
RL   Am. J. Med. Genet. A 143A:1212-1217(2007).
RN   [43]
RP   VARIANTS [LARGE SCALE ANALYSIS] ASP-149; CYS-378; ALA-494; SER-527;
RP   SER-641; TYR-868; ILE-1010; GLN-1031; ASN-1049; GLN-1075 AND HIS-1146.
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   [44]
RP   VARIANT LMPHM1 THR-855, AND CHARACTERIZATION OF VARIANT LMPHM1 THR-855.
RX   PubMed=19289394; DOI=10.1136/jmg.2008.064469;
RA   Ghalamkarpour A., Holnthoner W., Saharinen P., Boon L.M., Mulliken J.B.,
RA   Alitalo K., Vikkula M.;
RT   "Recessive primary congenital lymphoedema caused by a VEGFR3 mutation.";
RL   J. Med. Genet. 46:399-404(2009).
RN   [45]
RP   VARIANT LMPHM1 CYS-1235.
RX   PubMed=26091405; DOI=10.1089/lrb.2014.0044;
RA   Melikhan-Revzin S., Kurolap A., Dagan E., Mory A., Gershoni-Baruch R.;
RT   "A novel missense mutation in FLT4 causes autosomal recessive hereditary
RT   lymphedema.";
RL   Lymphat. Res. Biol. 13:107-111(2015).
RN   [46]
RP   VARIANTS CHTD7 82-ARG--TYR-1363 DEL; 361-TYR--TYR-1363 DEL;
RP   736-GLN--TYR-1363 DEL AND 999-GLN--TYR-1363 DEL, AND INVOLVEMENT IN CHTD7.
RX   PubMed=28991257; DOI=10.1038/ng.3970;
RA   Jin S.C., Homsy J., Zaidi S., Lu Q., Morton S., DePalma S.R., Zeng X.,
RA   Qi H., Chang W., Sierant M.C., Hung W.C., Haider S., Zhang J., Knight J.,
RA   Bjornson R.D., Castaldi C., Tikhonoa I.R., Bilguvar K., Mane S.M.,
RA   Sanders S.J., Mital S., Russell M.W., Gaynor J.W., Deanfield J.,
RA   Giardini A., Porter G.A. Jr., Srivastava D., Lo C.W., Shen Y.,
RA   Watkins W.S., Yandell M., Yost H.J., Tristani-Firouzi M., Newburger J.W.,
RA   Roberts A.E., Kim R., Zhao H., Kaltman J.R., Goldmuntz E., Chung W.K.,
RA   Seidman J.G., Gelb B.D., Seidman C.E., Lifton R.P., Brueckner M.;
RT   "Contribution of rare inherited and de novo variants in 2,871 congenital
RT   heart disease probands.";
RL   Nat. Genet. 49:1593-1601(2017).
RN   [47]
RP   VARIANTS CHTD7 GLU-741 DEL; 833-TYR--TYR-1363 DEL; VAL-1173 AND
RP   1192-GLN--TYR-1363 DEL, AND INVOLVEMENT IN CHTD7.
RX   PubMed=30232381; DOI=10.1038/s41436-018-0260-9;
RA   Reuter M.S., Jobling R., Chaturvedi R.R., Manshaei R., Costain G.,
RA   Heung T., Curtis M., Hosseini S.M., Liston E., Lowther C., Oechslin E.,
RA   Sticht H., Thiruvahindrapuram B., Mil S.V., Wald R.M., Walker S.,
RA   Marshall C.R., Silversides C.K., Scherer S.W., Kim R.H., Bassett A.S.;
RT   "Haploinsufficiency of vascular endothelial growth factor related signaling
RT   genes is associated with tetralogy of Fallot.";
RL   Genet. Med. 21:1001-1007(2019).
CC   -!- FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor
CC       for VEGFC and VEGFD, and plays an essential role in adult
CC       lymphangiogenesis and in the development of the vascular network and
CC       the cardiovascular system during embryonic development. Promotes
CC       proliferation, survival and migration of endothelial cells, and
CC       regulates angiogenic sprouting. Signaling by activated FLT4 leads to
CC       enhanced production of VEGFC, and to a lesser degree VEGFA, thereby
CC       creating a positive feedback loop that enhances FLT4 signaling.
CC       Modulates KDR signaling by forming heterodimers. The secreted isoform 3
CC       may function as a decoy receptor for VEGFC and/or VEGFD and play an
CC       important role as a negative regulator of VEGFC-mediated
CC       lymphangiogenesis and angiogenesis. Binding of vascular growth factors
CC       to isoform 1 or isoform 2 leads to the activation of several signaling
CC       cascades; isoform 2 seems to be less efficient in signal transduction,
CC       because it has a truncated C-terminus and therefore lacks several
CC       phosphorylation sites. Mediates activation of the MAPK1/ERK2,
CC       MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway,
CC       and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates
CC       phosphorylation of PIK3R1, the regulatory subunit of
CC       phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at
CC       'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'.
CC       {ECO:0000269|PubMed:11532940, ECO:0000269|PubMed:15102829,
CC       ECO:0000269|PubMed:15474514, ECO:0000269|PubMed:16076871,
CC       ECO:0000269|PubMed:16452200, ECO:0000269|PubMed:17210781,
CC       ECO:0000269|PubMed:19610651, ECO:0000269|PubMed:19779139,
CC       ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20431062,
CC       ECO:0000269|PubMed:20445537, ECO:0000269|PubMed:21273538,
CC       ECO:0000269|PubMed:7675451, ECO:0000269|PubMed:8700872,
CC       ECO:0000269|PubMed:9435229}.
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:12881528, ECO:0000269|PubMed:7898938};
CC   -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence
CC       of bound ligand. Binding of VEGFC or VEGFD leads to dimerization and
CC       activation by autophosphorylation on tyrosine residues. Inhibited by
CC       MAZ51. {ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:19779139,
CC       ECO:0000269|PubMed:20431062}.
CC   -!- SUBUNIT: Interacts with VEGFC and VEGFD. Monomer in the absence of
CC       bound VEGFC or VEGFD. Homodimer in the presence of bound VEGFC or
CC       VEGFD. Can also form a heterodimer with KDR. Interacts with PTPN14; the
CC       interaction is enhanced by stimulation with VEGFC. Interacts with CRK,
CC       GRB2, PTK2/FAK1, SHC1, PIK3R1 and PTPN11/SHP-2. Identified in a complex
CC       with SRC and ITGB1. {ECO:0000269|PubMed:12881528,
CC       ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:15474514,
CC       ECO:0000269|PubMed:16076871, ECO:0000269|PubMed:16452200,
CC       ECO:0000269|PubMed:18593464, ECO:0000269|PubMed:19610651,
CC       ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20431062,
CC       ECO:0000269|PubMed:20826270, ECO:0000269|PubMed:23878260,
CC       ECO:0000269|PubMed:7675451, ECO:0000269|PubMed:8700872,
CC       ECO:0000269|PubMed:9435229}.
CC   -!- INTERACTION:
CC       P35916; P08238: HSP90AB1; NbExp=3; IntAct=EBI-1005467, EBI-352572;
CC       P35916; P35968: KDR; NbExp=5; IntAct=EBI-1005467, EBI-1005487;
CC       P35916; P49767: VEGFC; NbExp=2; IntAct=EBI-1005467, EBI-3405539;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20445537,
CC       ECO:0000269|PubMed:7898938}; Single-pass type I membrane protein.
CC       Cytoplasm {ECO:0000269|PubMed:16452200, ECO:0000269|PubMed:20445537}.
CC       Nucleus {ECO:0000269|PubMed:16452200}. Note=Ligand-mediated
CC       autophosphorylation leads to rapid internalization.
CC       {ECO:0000269|PubMed:20445537}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I
CC       membrane protein. Note=Ligand-mediated autophosphorylation leads to
CC       rapid internalization.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane; Single-pass type I
CC       membrane protein.
CC   -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted. Cytoplasm.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1; Synonyms=Long;
CC         IsoId=P35916-2; Sequence=Displayed;
CC       Name=2; Synonyms=Short;
CC         IsoId=P35916-1; Sequence=VSP_041995;
CC       Name=3; Synonyms=sVegfr3;
CC         IsoId=P35916-3; Sequence=VSP_041993, VSP_041994;
CC   -!- TISSUE SPECIFICITY: Detected in endothelial cells (at protein level).
CC       Widely expressed. Detected in fetal spleen, lung and brain. Detected in
CC       adult liver, muscle, thymus, placenta, lung, testis, ovary, prostate,
CC       heart, and kidney. {ECO:0000269|PubMed:1327515,
CC       ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:7675451}.
CC   -!- DOMAIN: The first and second Ig-like C2-type (immunoglobulin-like)
CC       domains are sufficient for VEGFC binding (PubMed:23878260). The fourth
CC       and fifth Ig-like C2-type domains are sufficient for homodimerization
CC       (PubMed:23878260). The fifth and seventh Ig-like C2-type domains are
CC       required for autophosphorylation and further activation
CC       (PubMed:23878260). {ECO:0000269|PubMed:23878260}.
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 in response to H(2)O(2) is mediated by a process that
CC       requires SRC and PRKCD activity. Phosphorylation at Tyr-1068 is
CC       required for autophosphorylation at additional tyrosine residues.
CC       Phosphorylation at Tyr-1063 and Tyr-1337 is important for interaction
CC       with CRK and subsequent activation of MAPK8. Phosphorylation at Tyr-
CC       1230, Tyr-1231 and Tyr-1337 is important for interaction with GRB2 and
CC       subsequent activation of the AKT1 and MAPK1/ERK2 and/or MAPK3/ERK1
CC       signaling pathways. In response to endothelial cell adhesion onto
CC       collagen, can also be phosphorylated in the absence of FLT4 kinase
CC       activity by SRC at Tyr-830, Tyr-833, Tyr-853, Tyr-1063, Tyr-1333, and
CC       Tyr-1337. {ECO:0000269|PubMed:12881528, ECO:0000269|PubMed:15102829,
CC       ECO:0000269|PubMed:15474514, ECO:0000269|PubMed:16076871,
CC       ECO:0000269|PubMed:20431062, ECO:0000269|PubMed:23878260,
CC       ECO:0000269|PubMed:8700872}.
CC   -!- DISEASE: Lymphatic malformation 1 (LMPHM1) [MIM:153100]: A form of
CC       primary lymphedema, a disease characterized by swelling of body parts
CC       due to developmental anomalies and functional defects of the lymphatic
CC       system. Patients with lymphedema may suffer from recurrent local
CC       infections. LMPHM1 is an autosomal dominant form with variable
CC       expression and severity. Onset is usually at birth or in early
CC       childhood but can occur later. Affected individuals manifest
CC       lymphedema, predominantly in the lower limbs, and hypoplasia of
CC       lymphatic vessels. Additional features are hemangioma and nail
CC       dysplasia or papillomatosis. {ECO:0000269|PubMed:10835628,
CC       ECO:0000269|PubMed:10856194, ECO:0000269|PubMed:12881528,
CC       ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:16924388,
CC       ECO:0000269|PubMed:16965327, ECO:0000269|PubMed:17458866,
CC       ECO:0000269|PubMed:19289394, ECO:0000269|PubMed:26091405,
CC       ECO:0000269|PubMed:9817924}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
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}. Note=Disease susceptibility is
CC       associated with variants affecting the gene represented in this entry.
CC   -!- DISEASE: Note=Plays an important role in tumor lymphangiogenesis, in
CC       cancer cell survival, migration, and formation of metastases.
CC   -!- DISEASE: Congenital heart defects, multiple types, 7 (CHTD7)
CC       [MIM:618780]: An autosomal dominant disorder with incomplete penetrance
CC       characterized by congenital developmental abnormalities involving
CC       structures of the heart. Common defects include tetralogy of Fallot,
CC       pulmonary stenosis or atresia, absent pulmonary valve, right aortic
CC       arch, double aortic arch, and major aortopulmonary collateral arteries.
CC       {ECO:0000269|PubMed:28991257, ECO:0000269|PubMed:30232381}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
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   -!- SEQUENCE CAUTION:
CC       Sequence=CAA48290.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=FLT4 entry;
CC       URL="https://en.wikipedia.org/wiki/FLT4";
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DR   EMBL; X69878; CAA49505.1; -; mRNA.
DR   EMBL; U43143; AAA85215.1; -; mRNA.
DR   EMBL; EU826564; ACF47600.1; -; mRNA.
DR   EMBL; AY233382; AAO89504.1; -; mRNA.
DR   EMBL; AY233383; AAO89505.1; -; mRNA.
DR   EMBL; AK291679; BAF84368.1; -; mRNA.
DR   EMBL; AC122714; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; X68203; CAA48290.1; ALT_INIT; mRNA.
DR   EMBL; S66407; AAB28539.1; -; mRNA.
DR   CCDS; CCDS43412.1; -. [P35916-1]
DR   CCDS; CCDS4457.1; -. [P35916-2]
DR   PIR; A48999; A48999.
DR   RefSeq; NP_002011.2; NM_002020.4. [P35916-1]
DR   RefSeq; NP_891555.2; NM_182925.4. [P35916-2]
DR   PDB; 4BSJ; X-ray; 2.50 A; A=330-553.
DR   PDB; 4BSK; X-ray; 4.20 A; A=23-229.
DR   PDBsum; 4BSJ; -.
DR   PDBsum; 4BSK; -.
DR   AlphaFoldDB; P35916; -.
DR   SMR; P35916; -.
DR   BioGRID; 108612; 250.
DR   CORUM; P35916; -.
DR   DIP; DIP-5739N; -.
DR   IntAct; P35916; 232.
DR   MINT; P35916; -.
DR   STRING; 9606.ENSP00000261937; -.
DR   BindingDB; P35916; -.
DR   ChEMBL; CHEMBL1955; -.
DR   DrugBank; DB06626; Axitinib.
DR   DrugBank; DB05932; Denibulin.
DR   DrugBank; DB12010; Fostamatinib.
DR   DrugBank; DB06101; IMC-1C11.
DR   DrugBank; DB09078; Lenvatinib.
DR   DrugBank; DB06080; Linifanib.
DR   DrugBank; DB09079; Nintedanib.
DR   DrugBank; DB06589; Pazopanib.
DR   DrugBank; DB08896; Regorafenib.
DR   DrugBank; DB15685; Selpercatinib.
DR   DrugBank; DB00398; Sorafenib.
DR   DrugBank; DB01268; Sunitinib.
DR   DrugBank; DB05075; TG-100801.
DR   DrugBank; DB11800; Tivozanib.
DR   DrugBank; DB04879; Vatalanib.
DR   DrugCentral; P35916; -.
DR   GuidetoPHARMACOLOGY; 1814; -.
DR   TCDB; 8.A.23.1.43; the basigin (basigin) family.
DR   GlyCosmos; P35916; 12 sites, No reported glycans.
DR   GlyGen; P35916; 12 sites.
DR   iPTMnet; P35916; -.
DR   PhosphoSitePlus; P35916; -.
DR   BioMuta; FLT4; -.
DR   DMDM; 357529070; -.
DR   jPOST; P35916; -.
DR   MassIVE; P35916; -.
DR   PaxDb; 9606-ENSP00000261937; -.
DR   PeptideAtlas; P35916; -.
DR   ProteomicsDB; 55166; -. [P35916-2]
DR   ProteomicsDB; 55167; -. [P35916-1]
DR   ProteomicsDB; 55168; -. [P35916-3]
DR   Antibodypedia; 3429; 1180 antibodies from 45 providers.
DR   DNASU; 2324; -.
DR   Ensembl; ENST00000261937.11; ENSP00000261937.6; ENSG00000037280.16. [P35916-2]
DR   Ensembl; ENST00000393347.7; ENSP00000377016.3; ENSG00000037280.16. [P35916-1]
DR   GeneID; 2324; -.
DR   KEGG; hsa:2324; -.
DR   MANE-Select; ENST00000261937.11; ENSP00000261937.6; NM_182925.5; NP_891555.2.
DR   UCSC; uc003mlz.4; human. [P35916-2]
DR   AGR; HGNC:3767; -.
DR   CTD; 2324; -.
DR   DisGeNET; 2324; -.
DR   GeneCards; FLT4; -.
DR   GeneReviews; FLT4; -.
DR   HGNC; HGNC:3767; FLT4.
DR   HPA; ENSG00000037280; Low tissue specificity.
DR   MalaCards; FLT4; -.
DR   MIM; 136352; gene.
DR   MIM; 153100; phenotype.
DR   MIM; 602089; phenotype.
DR   MIM; 618780; phenotype.
DR   neXtProt; NX_P35916; -.
DR   OpenTargets; ENSG00000037280; -.
DR   Orphanet; 79452; Milroy disease.
DR   Orphanet; 464293; NON RARE IN EUROPE: Infantile capillary hemangioma.
DR   Orphanet; 3303; Tetralogy of Fallot.
DR   PharmGKB; PA28183; -.
DR   VEuPathDB; HostDB:ENSG00000037280; -.
DR   eggNOG; KOG0200; Eukaryota.
DR   GeneTree; ENSGT00940000159358; -.
DR   HOGENOM; CLU_000288_49_4_1; -.
DR   InParanoid; P35916; -.
DR   OMA; WDDRQGM; -.
DR   OrthoDB; 1614410at2759; -.
DR   PhylomeDB; P35916; -.
DR   TreeFam; TF325768; -.
DR   BRENDA; 2.7.10.1; 2681.
DR   PathwayCommons; P35916; -.
DR   Reactome; R-HSA-195399; VEGF binds to VEGFR leading to receptor dimerization.
DR   Reactome; R-HSA-9013695; NOTCH4 Intracellular Domain Regulates Transcription.
DR   SignaLink; P35916; -.
DR   SIGNOR; P35916; -.
DR   BioGRID-ORCS; 2324; 12 hits in 1191 CRISPR screens.
DR   ChiTaRS; FLT4; human.
DR   GeneWiki; FLT4; -.
DR   GenomeRNAi; 2324; -.
DR   Pharos; P35916; Tclin.
DR   PRO; PR:P35916; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; P35916; Protein.
DR   Bgee; ENSG00000037280; Expressed in right lobe of thyroid gland and 104 other cell types or tissues.
DR   ExpressionAtlas; P35916; baseline and differential.
DR   Genevisible; P35916; HS.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0043235; C:receptor complex; IDA:MGI.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0019838; F:growth factor binding; IPI:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
DR   GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IMP:UniProtKB.
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:0048514; P:blood vessel morphogenesis; ISS:UniProtKB.
DR   GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IDA:UniProtKB.
DR   GO; GO:0048286; P:lung alveolus development; IEA:Ensembl.
DR   GO; GO:0001945; P:lymph vessel development; ISS:BHF-UCL.
DR   GO; GO:0001946; P:lymphangiogenesis; IMP:UniProtKB.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR   GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR   GO; GO:0030335; P:positive regulation of cell migration; IBA:GO_Central.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR   GO; GO:0010595; P:positive regulation of endothelial cell migration; IMP:UniProtKB.
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:0046330; P:positive regulation of JNK cascade; IMP:UniProtKB.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:UniProtKB.
DR   GO; GO:0090037; P:positive regulation of protein kinase C signaling; IMP:UniProtKB.
DR   GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
DR   GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; IMP:UniProtKB.
DR   GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR   GO; GO:0060312; P:regulation of blood vessel remodeling; ISS:UniProtKB.
DR   GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR   GO; GO:0003016; P:respiratory system process; IEA:Ensembl.
DR   GO; GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB.
DR   GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; TAS:ProtInc.
DR   GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IDA:MGI.
DR   GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0001944; P:vasculature development; ISS:UniProtKB.
DR   CDD; cd00096; Ig; 1.
DR   CDD; cd05862; IgI_VEGFR; 1.
DR   CDD; cd05863; IgI_VEGFR-3; 1.
DR   CDD; cd05102; PTKc_VEGFR3; 1.
DR   DisProt; DP02600; -.
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   PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
DR   PANTHER; PTHR24416:SF49; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 3; 1.
DR   Pfam; PF07679; I-set; 1.
DR   Pfam; PF00047; ig; 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; PR01835; VEGFRECEPTR3.
DR   SMART; SM00409; IG; 6.
DR   SMART; SM00408; IGc2; 4.
DR   SMART; SM00219; TyrKc; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 6.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS50835; IG_LIKE; 6.
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 membrane; Cytoplasm; Direct protein sequencing; Disease variant;
KW   Disulfide bond; Glycoprotein; Immunoglobulin domain; Kinase; Membrane;
KW   Nucleotide-binding; Nucleus; Phosphoprotein; Receptor; Reference proteome;
KW   Repeat; Secreted; Signal; Transferase; Transmembrane; Transmembrane helix;
KW   Tyrosine-protein kinase.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000269|PubMed:15340161"
FT   CHAIN           25..1363
FT                   /note="Vascular endothelial growth factor receptor 3"
FT                   /id="PRO_0000016776"
FT   TOPO_DOM        25..775
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        776..796
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        797..1363
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          30..127
FT                   /note="Ig-like C2-type 1"
FT   DOMAIN          151..213
FT                   /note="Ig-like C2-type 2"
FT   DOMAIN          219..326
FT                   /note="Ig-like C2-type 3"
FT   DOMAIN          331..415
FT                   /note="Ig-like C2-type 4"
FT   DOMAIN          422..552
FT                   /note="Ig-like C2-type 5"
FT   DOMAIN          555..671
FT                   /note="Ig-like C2-type 6"
FT   DOMAIN          678..764
FT                   /note="Ig-like C2-type 7"
FT   DOMAIN          845..1173
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          1291..1331
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        1037
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10028"
FT   BINDING         851..859
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         879
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000305"
FT   MOD_RES         830
FT                   /note="Phosphotyrosine; by SRC"
FT                   /evidence="ECO:0000269|PubMed:20431062"
FT   MOD_RES         833
FT                   /note="Phosphotyrosine; by SRC"
FT                   /evidence="ECO:0000269|PubMed:20431062"
FT   MOD_RES         853
FT                   /note="Phosphotyrosine; by SRC"
FT                   /evidence="ECO:0000269|PubMed:20431062"
FT   MOD_RES         1063
FT                   /note="Phosphotyrosine; by autocatalysis and SRC"
FT                   /evidence="ECO:0000269|PubMed:16076871,
FT                   ECO:0000269|PubMed:20431062"
FT   MOD_RES         1068
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:16076871,
FT                   ECO:0000269|PubMed:20431062"
FT   MOD_RES         1230
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:12881528,
FT                   ECO:0000269|PubMed:16076871"
FT   MOD_RES         1231
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:12881528,
FT                   ECO:0000269|PubMed:16076871"
FT   MOD_RES         1265
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:12881528"
FT   MOD_RES         1333
FT                   /note="Phosphotyrosine; by autocatalysis and SRC"
FT                   /evidence="ECO:0000269|PubMed:12881528,
FT                   ECO:0000269|PubMed:20431062"
FT   MOD_RES         1337
FT                   /note="Phosphotyrosine; by autocatalysis and SRC"
FT                   /evidence="ECO:0000269|PubMed:12881528,
FT                   ECO:0000269|PubMed:16076871, ECO:0000269|PubMed:20431062"
FT   MOD_RES         1363
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:12881528"
FT   CARBOHYD        33
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:23878260,
FT                   ECO:0007744|PDB:4BSK"
FT   CARBOHYD        104
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:23878260,
FT                   ECO:0007744|PDB:4BSK"
FT   CARBOHYD        166
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        251
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        299
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        411
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:23878260,
FT                   ECO:0007744|PDB:4BSK"
FT   CARBOHYD        515
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:23878260,
FT                   ECO:0007744|PDB:4BSK"
FT   CARBOHYD        527
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16335952"
FT   CARBOHYD        594
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        683
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        690
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        758
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        51..111
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT                   ECO:0000269|PubMed:23878260"
FT   DISULFID        158..206
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT                   ECO:0000269|PubMed:23878260"
FT   DISULFID        252..310
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        445..534
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT                   ECO:0000269|PubMed:23878260"
FT   DISULFID        466..486
FT                   /evidence="ECO:0000269|PubMed:23878260"
FT   DISULFID        578..653
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        699..751
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   VAR_SEQ         724..765
FT                   /note="VDLADSNQKLSIQRVREEDAGRYLCSVCNAKGCVNSSASVAV -> REGGPG
FT                   EGQVRRPARPTIPNPGGPAPPPHPLQESTWRTPTRS (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:18593464"
FT                   /id="VSP_041993"
FT   VAR_SEQ         766..1298
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:18593464"
FT                   /id="VSP_041994"
FT   VAR_SEQ         1298..1363
FT                   /note="SCKGPGQNVAVTRAHPDSQGRRRRPERGARGGQVFYNSEYGELSEPSEEDHC
FT                   SPSARVTFFTDNSY -> R (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:1319394,
FT                   ECO:0000303|PubMed:1327515, ECO:0000303|PubMed:14702039,
FT                   ECO:0000303|PubMed:8386825, ECO:0000303|PubMed:8700872,
FT                   ECO:0000303|Ref.7"
FT                   /id="VSP_041995"
FT   VARIANT         82..1363
FT                   /note="Missing (in CHTD7)"
FT                   /evidence="ECO:0000269|PubMed:28991257"
FT                   /id="VAR_083806"
FT   VARIANT         149
FT                   /note="N -> D (in dbSNP:rs34221241)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042062"
FT   VARIANT         361..1363
FT                   /note="Missing (in CHTD7)"
FT                   /evidence="ECO:0000269|PubMed:28991257"
FT                   /id="VAR_083807"
FT   VARIANT         378
FT                   /note="R -> C (in a renal clear cell carcinoma sample;
FT                   somatic mutation; dbSNP:rs372947534)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042063"
FT   VARIANT         494
FT                   /note="T -> A (in dbSNP:rs307826)"
FT                   /evidence="ECO:0000269|PubMed:11807987,
FT                   ECO:0000269|PubMed:17344846"
FT                   /id="VAR_018407"
FT   VARIANT         527
FT                   /note="N -> S (in dbSNP:rs35874891)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_034379"
FT   VARIANT         641
FT                   /note="P -> S (in dbSNP:rs55667289)"
FT                   /evidence="ECO:0000269|PubMed:10835628,
FT                   ECO:0000269|PubMed:17344846"
FT                   /id="VAR_018408"
FT   VARIANT         736..1363
FT                   /note="Missing (in CHTD7)"
FT                   /evidence="ECO:0000269|PubMed:28991257"
FT                   /id="VAR_083808"
FT   VARIANT         741
FT                   /note="Missing (in CHTD7; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:30232381"
FT                   /id="VAR_083809"
FT   VARIANT         833..1363
FT                   /note="Missing (in CHTD7)"
FT                   /evidence="ECO:0000269|PubMed:30232381"
FT                   /id="VAR_083810"
FT   VARIANT         855
FT                   /note="A -> T (in LMPHM1; recessive form; results in
FT                   reduced autophosphorylation; results in impaired ligand-
FT                   induced receptor internalization and downstream signaling;
FT                   dbSNP:rs121909657)"
FT                   /evidence="ECO:0000269|PubMed:19289394"
FT                   /id="VAR_074044"
FT   VARIANT         857
FT                   /note="G -> R (in LMPHM1; loss of kinase activity;
FT                   dbSNP:rs267606818)"
FT                   /evidence="ECO:0000269|PubMed:10835628,
FT                   ECO:0000269|PubMed:15102829"
FT                   /id="VAR_018409"
FT   VARIANT         868
FT                   /note="H -> Y (in dbSNP:rs35171798)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042064"
FT   VARIANT         878
FT                   /note="V -> M (in LMPHM1; dbSNP:rs121909654)"
FT                   /evidence="ECO:0000269|PubMed:16965327"
FT                   /id="VAR_074045"
FT   VARIANT         890
FT                   /note="H -> Q (in dbSNP:rs448012)"
FT                   /evidence="ECO:0000269|PubMed:11807987,
FT                   ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:8386825,
FT                   ECO:0000269|Ref.7"
FT                   /id="VAR_018410"
FT   VARIANT         954
FT                   /note="P -> S (in HCI; dbSNP:rs34255532)"
FT                   /evidence="ECO:0000269|PubMed:11807987"
FT                   /id="VAR_018411"
FT   VARIANT         999..1363
FT                   /note="Missing (in CHTD7)"
FT                   /evidence="ECO:0000269|PubMed:28991257"
FT                   /id="VAR_083811"
FT   VARIANT         1010
FT                   /note="T -> I (in a metastatic melanoma sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042065"
FT   VARIANT         1020
FT                   /note="Q -> L (in LMPHM1)"
FT                   /evidence="ECO:0000269|PubMed:17458866"
FT                   /id="VAR_074046"
FT   VARIANT         1031
FT                   /note="R -> Q (in dbSNP:rs56082504)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042066"
FT   VARIANT         1035
FT                   /note="H -> Q (found in sporadic congenital lymphedema;
FT                   uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:16965327"
FT                   /id="VAR_074047"
FT   VARIANT         1035
FT                   /note="H -> R (in LMPHM1; loss of kinase activity;
FT                   dbSNP:rs121909653)"
FT                   /evidence="ECO:0000269|PubMed:10856194"
FT                   /id="VAR_018412"
FT   VARIANT         1041
FT                   /note="R -> P (in LMPHM1; loss of kinase activity;
FT                   dbSNP:rs121909650)"
FT                   /evidence="ECO:0000269|PubMed:10835628,
FT                   ECO:0000269|PubMed:12881528"
FT                   /id="VAR_018413"
FT   VARIANT         1044
FT                   /note="L -> P (in LMPHM1; loss of kinase activity;
FT                   dbSNP:rs121909651)"
FT                   /evidence="ECO:0000269|PubMed:10835628"
FT                   /id="VAR_018414"
FT   VARIANT         1049
FT                   /note="D -> N (in dbSNP:rs56310180)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042067"
FT   VARIANT         1075
FT                   /note="R -> Q (in dbSNP:rs1400220848)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042068"
FT   VARIANT         1086
FT                   /note="I -> T (in LMPHM1; dbSNP:rs121909655)"
FT                   /evidence="ECO:0000269|PubMed:16965327"
FT                   /id="VAR_074048"
FT   VARIANT         1106
FT                   /note="E -> K (in LMPHM1; dbSNP:rs121909656)"
FT                   /evidence="ECO:0000269|PubMed:16924388"
FT                   /id="VAR_074049"
FT   VARIANT         1108
FT                   /note="Missing (in LMPHM1)"
FT                   /evidence="ECO:0000269|PubMed:16965327"
FT                   /id="VAR_074050"
FT   VARIANT         1114
FT                   /note="P -> L (in LMPHM1; loss of kinase activity;
FT                   dbSNP:rs121909652)"
FT                   /evidence="ECO:0000269|PubMed:10835628,
FT                   ECO:0000269|PubMed:9817924"
FT                   /id="VAR_018415"
FT   VARIANT         1137
FT                   /note="P -> S (in HCI)"
FT                   /evidence="ECO:0000269|PubMed:11807987"
FT                   /id="VAR_018416"
FT   VARIANT         1146
FT                   /note="R -> H (in dbSNP:rs1130379)"
FT                   /evidence="ECO:0000269|PubMed:11807987,
FT                   ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:8386825,
FT                   ECO:0000269|Ref.7"
FT                   /id="VAR_018417"
FT   VARIANT         1173
FT                   /note="L -> V (in CHTD7; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:30232381"
FT                   /id="VAR_083812"
FT   VARIANT         1192..1363
FT                   /note="Missing (in CHTD7)"
FT                   /evidence="ECO:0000269|PubMed:30232381"
FT                   /id="VAR_083813"
FT   VARIANT         1235
FT                   /note="S -> C (in LMPHM1; recessive form)"
FT                   /evidence="ECO:0000269|PubMed:26091405"
FT                   /id="VAR_074051"
FT   MUTAGEN         446
FT                   /note="T->E: Decreases autophosphorylation on tyrosine
FT                   residues upon ligand binding; when associated with A-516.
FT                   Abolishes autophosphorylation on tyrosine residues upon
FT                   ligand binding; when associated with A-516 and A-737."
FT                   /evidence="ECO:0000269|PubMed:23878260"
FT   MUTAGEN         516
FT                   /note="K->A: Decreases autophosphorylation on tyrosine
FT                   residues upon ligand binding; when associated with E-446.
FT                   Abolishes autophosphorylation on tyrosine residues upon
FT                   ligand binding; when associated with E-446 and A-737."
FT                   /evidence="ECO:0000269|PubMed:23878260"
FT   MUTAGEN         737
FT                   /note="R->A: Decreases autophosphorylation on tyrosine
FT                   residues upon ligand binding. Abolishes autophosphorylation
FT                   on tyrosine residues upon ligand binding; when associated
FT                   with E-446 and A-516."
FT                   /evidence="ECO:0000269|PubMed:23878260"
FT   MUTAGEN         879
FT                   /note="K->G: Abolishes enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:12881528"
FT   MUTAGEN         1063
FT                   /note="Y->F: Loss of phosphorylation site. No effect on
FT                   stimulation of cell proliferation and cell migration."
FT                   /evidence="ECO:0000269|PubMed:16076871,
FT                   ECO:0000269|PubMed:20431062"
FT   MUTAGEN         1068
FT                   /note="Y->F: Global loss of autophosphorylation. Abolishes
FT                   stimulation of cell proliferation and cell migration."
FT                   /evidence="ECO:0000269|PubMed:16076871,
FT                   ECO:0000269|PubMed:20431062"
FT   MUTAGEN         1230
FT                   /note="Y->F: Loss of phosphorylation site. Strongly reduces
FT                   stimulation of cell proliferation and cell migration."
FT                   /evidence="ECO:0000269|PubMed:12881528,
FT                   ECO:0000269|PubMed:16076871"
FT   MUTAGEN         1231
FT                   /note="Y->F: Loss of phosphorylation site. Strongly reduces
FT                   stimulation of cell proliferation and cell migration."
FT                   /evidence="ECO:0000269|PubMed:12881528,
FT                   ECO:0000269|PubMed:16076871"
FT   MUTAGEN         1265
FT                   /note="Y->F: Loss of phosphorylation site. No effect on
FT                   stimulation of cell proliferation and cell migration."
FT                   /evidence="ECO:0000269|PubMed:12881528"
FT   MUTAGEN         1333
FT                   /note="Y->F: Loss of phosphorylation site. Reduced
FT                   autophosphorylation."
FT                   /evidence="ECO:0000269|PubMed:12881528,
FT                   ECO:0000269|PubMed:7675451"
FT   MUTAGEN         1337
FT                   /note="Y->F: Reduced autophosphorylation. Strongly reduces
FT                   stimulation of cell proliferation and cell migration."
FT                   /evidence="ECO:0000269|PubMed:12881528,
FT                   ECO:0000269|PubMed:20431062, ECO:0000269|PubMed:7675451"
FT   MUTAGEN         1363
FT                   /note="Y->F: Loss of phosphorylation site. Slightly reduced
FT                   autophosphorylation."
FT                   /evidence="ECO:0000269|PubMed:12881528,
FT                   ECO:0000269|PubMed:7675451"
FT   CONFLICT        24
FT                   /note="G -> D (in Ref. 3; CAA49505 and 7; AAO89504/
FT                   AAO89505)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        538
FT                   /note="N -> D (in Ref. 8; BAF84368)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        745
FT                   /note="R -> P (in Ref. 3; CAA49505 and 7; AAO89504/
FT                   AAO89505)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        752..753
FT                   /note="NA -> RP (in Ref. 3; CAA49505 and 7; AAO89504/
FT                   AAO89505)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1128
FT                   /note="L -> V (in Ref. 3; CAA49505 and 7; AAO89504/
FT                   AAO89505)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1164
FT                   /note="E -> D (in Ref. 3; CAA49505)"
FT                   /evidence="ECO:0000305"
FT   STRAND          332..339
FT                   /evidence="ECO:0007829|PDB:4BSJ"
FT   STRAND          341..346
FT                   /evidence="ECO:0007829|PDB:4BSJ"
FT   STRAND          350..362
FT                   /evidence="ECO:0007829|PDB:4BSJ"
FT   STRAND          365..370
FT                   /evidence="ECO:0007829|PDB:4BSJ"
FT   STRAND          381..388
FT                   /evidence="ECO:0007829|PDB:4BSJ"
FT   HELIX           391..393
FT                   /evidence="ECO:0007829|PDB:4BSJ"
FT   STRAND          395..403
FT                   /evidence="ECO:0007829|PDB:4BSJ"
FT   TURN            404..407
FT                   /evidence="ECO:0007829|PDB:4BSJ"
FT   STRAND          408..424
FT                   /evidence="ECO:0007829|PDB:4BSJ"
FT   HELIX           425..428
FT                   /evidence="ECO:0007829|PDB:4BSJ"
FT   STRAND          441..451
FT                   /evidence="ECO:0007829|PDB:4BSJ"
FT   STRAND          457..464
FT                   /evidence="ECO:0007829|PDB:4BSJ"
FT   STRAND          501..511
FT                   /evidence="ECO:0007829|PDB:4BSJ"
FT   STRAND          514..524
FT                   /evidence="ECO:0007829|PDB:4BSJ"
FT   STRAND          530..538
FT                   /evidence="ECO:0007829|PDB:4BSJ"
FT   STRAND          541..549
FT                   /evidence="ECO:0007829|PDB:4BSJ"
SQ   SEQUENCE   1363 AA;  152757 MW;  B1473AAAC95E7E93 CRC64;
     MQRGAALCLR LWLCLGLLDG LVSGYSMTPP TLNITEESHV IDTGDSLSIS CRGQHPLEWA
     WPGAQEAPAT GDKDSEDTGV VRDCEGTDAR PYCKVLLLHE VHANDTGSYV CYYKYIKARI
     EGTTAASSYV FVRDFEQPFI NKPDTLLVNR KDAMWVPCLV SIPGLNVTLR SQSSVLWPDG
     QEVVWDDRRG MLVSTPLLHD ALYLQCETTW GDQDFLSNPF LVHITGNELY DIQLLPRKSL
     ELLVGEKLVL NCTVWAEFNS GVTFDWDYPG KQAERGKWVP ERRSQQTHTE LSSILTIHNV
     SQHDLGSYVC KANNGIQRFR ESTEVIVHEN PFISVEWLKG PILEATAGDE LVKLPVKLAA
     YPPPEFQWYK DGKALSGRHS PHALVLKEVT EASTGTYTLA LWNSAAGLRR NISLELVVNV
     PPQIHEKEAS SPSIYSRHSR QALTCTAYGV PLPLSIQWHW RPWTPCKMFA QRSLRRRQQQ
     DLMPQCRDWR AVTTQDAVNP IESLDTWTEF VEGKNKTVSK LVIQNANVSA MYKCVVSNKV
     GQDERLIYFY VTTIPDGFTI ESKPSEELLE GQPVLLSCQA DSYKYEHLRW YRLNLSTLHD
     AHGNPLLLDC KNVHLFATPL AASLEEVAPG ARHATLSLSI PRVAPEHEGH YVCEVQDRRS
     HDKHCHKKYL SVQALEAPRL TQNLTDLLVN VSDSLEMQCL VAGAHAPSIV WYKDERLLEE
     KSGVDLADSN QKLSIQRVRE EDAGRYLCSV CNAKGCVNSS ASVAVEGSED KGSMEIVILV
     GTGVIAVFFW VLLLLIFCNM RRPAHADIKT GYLSIIMDPG EVPLEEQCEY LSYDASQWEF
     PRERLHLGRV LGYGAFGKVV EASAFGIHKG SSCDTVAVKM LKEGATASEH RALMSELKIL
     IHIGNHLNVV NLLGACTKPQ GPLMVIVEFC KYGNLSNFLR AKRDAFSPCA EKSPEQRGRF
     RAMVELARLD RRRPGSSDRV LFARFSKTEG GARRASPDQE AEDLWLSPLT MEDLVCYSFQ
     VARGMEFLAS RKCIHRDLAA RNILLSESDV VKICDFGLAR DIYKDPDYVR KGSARLPLKW
     MAPESIFDKV YTTQSDVWSF GVLLWEIFSL GASPYPGVQI NEEFCQRLRD GTRMRAPELA
     TPAIRRIMLN CWSGDPKARP AFSELVEILG DLLQGRGLQE EEEVCMAPRS SQSSEEGSFS
     QVSTMALHIA QADAEDSPPS LQRHSLAARY YNWVSFPGCL ARGAETRGSS RMKTFEEFPM
     TPTTYKGSVD NQTDSGMVLA SEEFEQIESR HRQESGFSCK GPGQNVAVTR AHPDSQGRRR
     RPERGARGGQ VFYNSEYGEL SEPSEEDHCS PSARVTFFTD NSY
//
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